There are doubts regarding the efficacy of calcium or vitamin D administered in monotherapy for the treatment of osteoporosis; they point out that "administered together they seem to have a certain degree of efficacy in the prevention of non-vertebral fractures, which is clearer in people who are deficient in them, as may be the case of elderly people living in residences. There is practically no evidence of their efficacy in the prevention of vertebral fractures.

79-year-old woman admitted for an osteoporotic hip fracture. Regarding secondary prevention of fragility fractures, point out the WRONG answer:

Low adherence to treatment is associated with an increased risk of fracture.

Bone remodeling markers may be useful for early monitoring of response to treatment.

Vitamin D monotherapy is effective in reducing these fractures in non-institutionalized elderly people.

Increasing dietary calcium or taking calcium supplements in isolation does not protect against the occurrence of fractures.

Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people.

For a 50-year old caucasian woman today, the risk of a hip fracture over her remaining lifetime is about 17%. Tomorrow the situation will clearly be worse because the continual increase in life expectancy will cause a 3-fold rise in worldwide fracture incidence over the next 60 years, particularly in women, but also in men. In addition, a secular increase in the incidence of hip fractures in individuals of the same age has been noted in both sexes by several investigators, and the cost of hip fractures is expected to dramatically increase in the next decades. Consequently, preventive strategies are urgently required. A great deal has been learned in recent years about the risk factors for hip fracture, the pathophysiology of this fracture, and the prediction of fracture risk, particularly through bone mass measurements on the hip and biochemical evaluations of parathyroid and vitamin D status. The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. A substantial femoral bone loss continues throughout the old age, with a continuous and exponential increase in the risk of hip fracture, and any reduction or arrest of this loss will induce an important reduction in the incidence of hip fractures. A preventive effect on the risk of hip fracture may be partly achieved by using long term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for a late prevention in elderly people. Vitamin D insufficiency and deficit in calcium intake are very common in elderly people living either in institutions or at home, particularly in Europe where dairy products are not fortified with vitamin D. The cumulative response to this deficit in calcium intake and low vitamin D status is a negative calcium balance which stimulates parathyroid hormone secretion. In 300 residents of nursing homes, we recently found a significant negative correlation between serum 25 OHD and log serum PTH after age-adjustment. In addition, in 446 elderly women living at home in 5 French cities and selected from the voting lists, we also found an age-adjusted relationship between serum 25 OHD and PTH concentrations. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of these supplements (1.2 g of calcium and 800 IU of vitamin D3) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced of 23% (intention-to-treat analysis) the number of hip fractures and other non vertebral fractures. In parallel, serum perathyroid hormone concentration was reduced of 28% and low serum 25-hydroxyvitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased 2.7% the vitamin D3-calcium group and decreased 4.6% in the placebo group (p < 0.001). This prevention is safe and can be recommended in people living in institutions. It could be also useful in other elderly subjects particularly at risk because of a low calcium intake, an absence of solar exposure and a previous history of falls. From the data of our study we assessed the economic consequences in terms of medical cost of this prevention. In case of treatment of all women living in nursing homes in France, this would saved FF 150000000 per year, the economic balance of prevention becoming positive as soon as the age of the beginning of the prevention reaches 73.5 years. It is now possible to partly stop bone loss in elderly people and it is never too late to prevent hip fractures with calcium and vitamin D supplements.

Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study.

Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people. Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures, as proved by Decalyos I. Decalyos II is a 2-year, multicenter, randomized, double-masked, placebo-controlled confirmatory study. The intention-to-treat population consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD = 7.1) randomized to the calcium-vitamin D3 fixed combination group (n = 199); the calcium plus vitamin D3 separate combination group (n = 190) and the placebo group (n = 194). Fixed and separate combination groups received the same daily amount of calcium (1200 mg) and vitamin D3 (800 IU), which had similar pharmacodynamic effects. Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent, with levels returning within the normal range after 6 months. In a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in the placebo group (mean = -2.36% per year, SD = 4.92), while remaining unchanged in women treated with calcium-vitamin D3 (mean = 0.29% per year, SD = 8.63). The difference between the two groups was 2.65% (95% CI = -0.44, 5.75%) with a trend in favor of the active treatment group. No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis. The relative risk (RR) of HF in the placebo group compared with the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women.

Prevention of hip fractures.

For a 50-year old Caucasian woman today, the risk of a hip fracture over her remaining life-time is about 17%. Tomorrow the situation will clearly be worse because the continuous increase in life expectancy will cause a three-fold increase in worldwide fracture incidence over the next 60 years. Through diagnostic bone mass measurements at the hip and assessment of biochemical parameters, a great deal has been learned in recent years about reduction of hip fracture risk. Preventive strategies are based on prevention of falls, use of hip protectors, and prevention of bone fragility. The latter includes the optimization of peak bone mass during childhood, postmenopausal estrogen replacement therapy, and also late prevention consisting in reversing senile secondary hyperparathyroidism, which plays an important role in the decrease of skeletal strength. This secondary hyperparathyroidism, which results from both vitamin D insufficiency and low calcium intake, is preventable with vitamin D3 and calcium supplements. They have recently been shown capable of providing effective prevention of hip fractures in elderly women living in nursing homes, with a reduction of about 25% in the number of hip fractures noted in a 3-year controlled study in 3,270 women (intention-to-treat analysis). In conclusion, it is never too early to reduce the risk of osteoporosis and never too late to prevent hip fractures.

Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: a meta-analysis.

The efficacy of vitamin D(3) in preventing fractures and falls has been explored in a number of clinical trials. However, recent evidence revealed new questions about the adequate doses of vitamin D(3) supplementation and its efficacy in fracture prevention independent of calcium supplements for various types of fractures. To conduct a meta-analysis to estimate the effectiveness of 800 IU daily vitamin D(3) supplementation for increasing bone mineral density (BMD) and preventing fractures in postmenopausal women. Medline and EMBASE were searched for controlled trials comparing the effectiveness of cholecalciferol (vitamin D(3)) against placebo with or without background calcium supplementation in the treatment of postmenopausal women. Eight controlled trials evaluating the effect of vitamin D(3) supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D(3) (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D(3) with calcium supplementation showed beneficial effects on the incidence of non-vertebral (odds ratio [OR] 0.77, 95% credibility limit [CL] 0.6-0.93) and hip (OR 0.70, 95% CL 0.53-0.90) fractures, while the effects on non-vertebral-non-hip fractures (OR 0.84, 95% CL 0.67-1.04) % point increase) were associated with more uncertainty. Vitamin D(3) supplementation showed a 70% probability of being a better treatment than placebo for the prevention of non-vertebral fractures, hip fractures, and non-vertebral, non-hip fractures. Compared to calcium supplementation, vitamin D(3) plus calcium reduced non-vertebral fractures (OR 0.68, 95% CL 0.43-1.01) and non-vertebral, non-hip fractures (OR 0.64, 95% CL 0.38-0.99), but did not reduce hip fractures (OR 1.03, 95% CL 0.39-2.25). Key limitations to this analysis include a small number of studies and heterogeneity in the study populations. This meta-analysis supports the use of vitamin D3 of 800 IU daily to reduce the incidence of osteoporotic non-vertebral, hip, and non-vertebral-non-hip fractures in elderly women. Vitamin D(3) with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures.

Where do we stand on vitamin D?

A meta-analysis of primary prevention high-quality trials published in 2005 found that oral cholecalciferol (D3) in a daily dose of 700-800 IU or intermittently 100,000 IU every 4 months with or without calcium, should reduce both hip and non-vertebral fracture risk significantly compared to placebo. Trials that administered 400 IU vitamin D did not achieve fracture efficacy. Notably, there was a significant association between higher achieved 25-hydroxyvitamin D levels (25(OH)D) in the treatment groups and fracture efficacy: The minimal mean level where fracture efficacy was observed was 74 nmol/l (25(OH)D). Epidemiological data for bone density and lower extremity strength support this threshold, and high-quality trials that used 700 to 800 IU D3 suggested fall risk reduction by 35 to 65% in institutionalized and community-dwelling older individuals. However, since the 2005 meta-analysis, benefits of vitamin D on fracture and fall reduction have been questioned by results from several recent trials. This review proposes that the interpretation of these recent trials is hindered by different doses of vitamin D, different types of supplemental vitamin D (D3 or ergocalciferol D2), low adherence, concurrent use of supplements outside the study protocol, open study design, short follow-up, and/or different patient risk profiles including primary and secondary fracture prevention. In most recent trials, low adherence, the use of the relatively less potent D2, or a too low dose of D3 (400 IU) may have prohibited a shift of (25(OH)D) levels in the treatment groups to the desirable range of at least 75 nmol/l. In summary, from recent trials, two lesson may be learned: (1) Adherence less than 60% is insufficient to achieve fracture efficacy with daily 800 IU D3 plus calcium, (2) D2 in any application or any previously studied dose may not reduce fractures in institutionalized or community-dwelling older individuals.

Reducing fracture risk with calcium and vitamin D.

Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance. This study tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. Calcium and vitamin D therapy has been recommended for older persons, either frail and institutionalized or independent, with key risk factors including decreased bone mineral density (BMD), osteoporotic fractures, increased bone remodelling as a result of secondary hyperparathyroidism and increased propensity to falls. In addition, treatment of osteoporosis with a bisphosphonate was less effective in patients with vitamin D deficiency. Calcium and vitamin D supplementation is a key component of prevention and treatment of osteoporosis unless calcium intake and vitamin D status are optimal. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, BMD, bone turnover, lower extremity function and falls, we suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50-75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in successful fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest. As calcium balance is not only affected by vitamin D status but also by calcium intake, recommendations for adequate calcium intake should also be met. The findings of community-based clinical trials with vitamin D and calcium supplementation in which compliance was moderate or less have often been negative, whereas studies in institutionalized patients in whom medication administration was supervised ensuring adequate compliance demonstrated significant benefits.

Treatment for osteoporosis in Australian residential aged care facilities: consensus recommendations for fracture prevention.

Older people living in residential aged care facilities (RACFs) are at considerably higher risk of suffering fractures than older people living in the community. When admitted to RACFs, patients should be assessed for fracture risk to ensure early implementation of effective fracture prevention measures. Routine or regular determination of calcium and phosphate serum levels in institutionalised older people is not indicated. Opinion is divided about the value of routine measurements of serum concentrations of 25-hydroxyvitamin D, parathyroid hormone and bone turnover markers. The non-pharmacological approach to fracture prevention includes multifactorial programs of falls prevention and the use of hip protectors. Vitamin D supplementation is recommended for all patients in RACFs. Dietary calcium intake should be optimised (1200-1500 mg per day is recommended) and supplementation offered to those with inadequate intake. The decision to prescribe calcium supplements should be guided by patients' tolerance, whether or not they have a history of kidney stones, and emerging data about its cardiovascular safety. Bisphosphonates are the first-choice pharmacological agents for fracture prevention in older persons at high risk. Intravenous administration is as efficient as oral and has the significant advantage of better adherence. Use of strontium ranelate has not been tested on people in RACFs, but evidence in the "old-old" (those aged 75 years and older) suggests it could be a therapeutic option for fracture prevention in this setting. In general, teriparatide should not be considered as a first-line treatment for fracture prevention, particularly for people in RACFs.

Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis.

Whether calcium supplementation can reduce osteoporotic fractures is uncertain. We did a meta-analysis to include all the randomised trials in which calcium, or calcium in combination with vitamin D, was used to prevent fracture and osteoporotic bone loss. We identified 29 randomised trials (n=63 897) using electronic databases, supplemented by a hand-search of reference lists, review articles, and conference abstracts. All randomised trials that recruited people aged 50 years or older were eligible. The main outcomes were fractures of all types and percentage change of bone-mineral density from baseline. Data were pooled by use of a random-effect model. In trials that reported fracture as an outcome (17 trials, n=52 625), treatment was associated with a 12% risk reduction in fractures of all types (risk ratio 0.88, 95% CI 0.83-0.95; p=0.0004). In trials that reported bone-mineral density as an outcome (23 trials, n=41 419), the treatment was associated with a reduced rate of bone loss of 0.54% (0.35-0.73; p<0.0001) at the hip and 1.19% (0.76-1.61%; p<0.0001) in the spine. The fracture risk reduction was significantly greater (24%) in trials in which the compliance rate was high (p<0.0001). The treatment effect was better with calcium doses of 1200 mg or more than with doses less than 1200 mg (0.80 vs 0.94; p=0.006), and with vitamin D doses of 800 IU or more than with doses less than 800 IU (0.84 vs 0.87; p=0.03). Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older. For best therapeutic effect, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation).

[Are calcium and vitamin D supplements for everyone?: Pro].

Calcium and vitamin D are essential for the health of our bones and various scientific societies recommend an intake of 1,000 mg of calcium and 800 IU of vitamin D daily. Most people with osteoporosis do not eat food with this amount of calcium and also have insufficient levels of vitamin D, so supplements are recommended to provide osteoporotic patients with these amounts. Calcium supplements and vitamin D improve the effectiveness of anabolic and anti-catabolic agents and may have a small effect in reducing the number of fractures. Calcium supplements alone have not shown efficacy preventing fractures in patients with osteoporosis and may increase cardiovascular risk in healthy elderly women and is therefore not recommended for widespread use. Vitamin D supplements are recommended in persons with 25-OH vitamin D levels below 30 ng/ml, in particular the elderly and osteoporotic patients, due to its ability to halt the remodeling resulting from secondary hyperparathyroidism and reduce the loss of bone mass. Vitamin D supplements could help reduce falls and fractures in the institutionalized elderly. In addition, supplements of vitamin D may have other beneficial effects due to extra-osseous regulatory functions on the immune response and cell differentiation and proliferation that is associated with vitamin D. Trials begun in recent years clearly indicate a beneficial effect of vitamin D supplements on mortality, cardiovascular risk,development of tumors and prevention of infections.

Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.

Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.

Pharmacological treatment of osteoporosis in the oldest old.

The incidence of osteoporotic fractures increases with age. Consequently, the global prevalence of osteoporotic fractures will increase with the aging of the population. In old age, osteoporosis is associated with a substantial burden in terms of morbidity and mortality. Nevertheless, osteoporosis in old age continues to be underdiagnosed and undertreated. This may, at least partly, be explained by the fact that evidence of the antifracture efficacy of osteoporosis treatments comes mainly from randomized controlled trials in postmenopausal women with a mean age of 70-75 years. However, in the last years, subgroup analyses of these landmark trials have been published investigating the efficacy and safety of osteoporosis treatment in the very elderly. Based on this evidence, this narrative review discusses the pharmacological management of osteoporosis in the oldest old (≥80 years). Because of the high prevalence of calcium and/or vitamin D deficiency in old age, these supplements are essential in the management of osteoporosis in the elderly people. Adding antiresorptive or anabolic treatments or combinations, thereof, reduces the risk of vertebral fractures even more, at least in the elderly with documented osteoporosis. The reduction of hip fracture risk by antiresorptive treatments is less convincing, which may be explained by insufficient statistical power in some subanalyses and/or a higher impact of nonskeletal risk factors in the occurrence of hip fractures. Compared with younger individuals, a larger absolute risk reduction is observed in the elderly because of the higher baseline fracture risk. Therefore, the elderly will benefit more of treatment. In addition, current osteoporosis therapies also appear to be safe in the elderly. Although more research is required to further clarify the effect of osteoporosis drugs in the elderly, especially with respect to hip fractures, there is currently sufficient evidence to initiate appropriate treatment in the elderly with osteoporosis and osteoporotic fractures.

Osteoporosis

Studies of the benefits of supplementation with calcium and vitamin D are conflicting, possibly because most studies did not have people with low dietary intakes. A 2018 review by the USPSTF found low-quality evidence that the routine use of calcium and vitamin D supplements (or both supplements together) did not reduce the risk of having an osteoporotic fracture in male and female adults living in the community who had no known history of vitamin D deficiency, osteoporosis, or a fracture. The USPSTF does not recommend low dose supplementation (less than 1 g of calcium and 400 IU of vitamin D) in postmenopausal women as there does not appear to be a difference in fracture risk. A 2015 review found little data that supplementation of calcium decreases the risk of fractures. While some meta-analyses have found a benefit of vitamin D supplements combined with calcium for fractures, they did not find a benefit of vitamin D supplements (800 IU/day or less) alone. While supplementation does

Vitamin D

Bone health In general, no good evidence supports the commonly held belief that vitamin D supplements can help prevent osteoporosis. Its general use for prevention of this disease in those without vitamin D deficiency is thus likely not needed. For older people with osteoporosis, taking vitamin D with calcium may help prevent hip fractures, but it also slightly increases the risk of stomach and kidney problems. A study found that supplementation with 800 IU or more daily, in those older than 65 years was "somewhat favorable in the prevention of hip fracture and non-vertebral fracture". The effect is small or none for people living independently. Low serum vitamin D levels have been associated with falls, and low bone mineral density. Taking extra vitamin D, however, does not appear to change the risk.

Strategies for treatment to prevent fragility fractures in postmenopausal women.

The objective of treatment of osteoporosis is to decrease the risk of fractures in patients at high risk for a first or subsequent fracture. The efficacy of treatment will depend on the efficiency and level of implementation of clinical case finding to select patients at risk, the results of additional investigations, the efficacy, tolerance and safety of medical intervention and the adherence to treatment during follow-up. Each of these steps is critical in treatment in daily practice. Failure to consider one or another step can result in suboptimal fracture prevention or overtreatment. The aim of case finding is to identify patients for treatment, who have disease characteristics of patients in whom fracture prevention has been demonstrated in randomised controlled trials (RCTs). These include patients with a low-trauma hip or vertebral fracture, with a low bone mineral density (BMD) or with a high risk of fracture based on the presence of clinical risk factors (CRFs) for osteoporosis and fractures such as included in the FRAX case-finding algorithm, with or without BMD. Case finding starts clinically, with systematic or opportunistic doctor- and/or patient-driven evaluation for the presence of CRFs, but its implementation is low. Further investigations aim to assess the risk of fracture(s) and to have baseline measurements for the subsequent monitoring of treatment, to exclude diseases that mimic osteoporosis, to identify the cause of osteoporosis and contributory factors and to select the most appropriate treatment. Medical intervention consists of providing information about osteoporosis to the patient, lifestyle advice, optimalisation of calcium intake and vitamin D status, fall prevention to reduce fall risk, correction of reversible contributors to secondary osteoporosis and a wide array of drugs for prevention of a first or subsequent vertebral, hip and non-vertebral, non-hip fracture. Drug treatment is based on manipulation of bone remodelling by inhibiting bone resorption (bisphosphonates, selective oestrogen-receptor modulator (SERMs), calcitonin), stimulating bone formation (parathyroid hormone) or mixed effects (strontium ranelate). Follow-up allows to check tolerance and safety, to optimise adherence and to decide about adequacy of response, duration and switching of therapy.

Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence.

Osteoporotic fractures are an extremely common and serious health problem in the elderly. This article presents the rationale for calcium and vitamin D supplementation in the prevention and treatment of osteoporotic fractures and reviews the literature evidence on the efficacy of this strategy. Two musculoskeletal risk factors are implicated in osteoporotic fractures in the elderly: the loss of bone mass due to secondary hyperparathyroidism and the increased propensity to falls. Calcium and vitamin D reverse secondary hyperparathyroidism with resultant beneficial effects on bone mineral density (BMD). Additionally, calcium and vitamin D supplementation significantly improves body sway and lower extremity strength, reducing the risk of falls. The effects of combined calcium and vitamin D on parathyroid function and BMD provide a strong rationale for the use of this therapy in the prevention and treatment of osteoporosis and osteoporotic fractures. There is general agreement that, in patients with documented osteoporosis, calcium and vitamin D supplementation should be an integral component of the management strategy, along with antiresorptive or anabolic treatment. Frail elderly individuals constitute another major target population for calcium and vitamin D because evidence from randomized studies in institutionalized elderly subjects demonstrates that these supplements reduce osteoporotic fracture risk, particularly in the presence of dietary deficiencies. However, the results of trials in community-dwelling subjects have been equivocal. Within the primary-care setting, further research is required to establish appropriate target subgroups for calcium and vitamin D supplementation; overall, the data are consistent with a benefit individuals with insufficient calcium and/or vitamin D, although patients with documented osteoporosis will derive further benefit in terms of fracture prevention from the addition of an antiresorptive agent.

Vitamin D3 and calcium to prevent hip fractures in elderly women.

Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Canadian health claims for food

Research supporting the claim There is a significant body of evidence which establishes that high calcium intakes augment bone gain during growth, retards age-related bone loss, and reduces osteoporotic fracture risk. A meta-analysis study in 2007 assessed whether calcium supplementation can reduce osteoporotic fractures. The meta-analysis included all the randomized trials in which calcium, or calcium in combination with vitamin D, was used to prevent fracture and osteoporotic bone loss.

Can we stop bone loss and prevent hip fractures in the elderly?

The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. Substantial femoral bone loss continues throughout old age, with a continuous and exponential increase in the risk of hip fracture; thus any reduction or arrest of this loss will induce an important reduction in the incidence of hip fracture. Preventive measures may be achieved during childhood by increasing peak bone mass with calcium and exercise, by using long-term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for late prevention in the elderly. Vitamin D insufficiency and a deficit in calcium intake are very common in the elderly living either in institutions or at home and the cumulative response to these deficits is a negative calcium balance which stimulates parathyroid hormone secretion. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of supplements (1.2 g calcium and 800 IU vitamin D3) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced the number of hip fractures by 23% (intention-to-treat analysis). In parallel, serum parathyroid hormone concentrations were reduced by 28% and low baseline serum 25-hydroxyvitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased by 2.7% in the vitamin D3-calcium group and decreased by 4.6% in the placebo group (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Senile osteoporosis

Calcium and vitamin D3 intake from diet or supplementation are crucial in the ethiopathogenesis of this disease; therefore, the effective treatments should consist of non pharmacological methods (such as a modified diet with more calcium 1000–1500 mg/day and vitamin D3 intake of 600-800 IU/day, exercising, smoking cessation, and alcohol restriction), fall prevention, and individually chosen pharmacological intervention (antiresorptive agent like bisphosphonate or estrogen replacement therapy in women). Given bone fracture (hip, vertebrae, and colles) is a devastating complication of osteoporosis, vitamin D3 combined with calcium are used as primary prevention, along with alendronate, residronate, strontium and zoledronic acid which have proven efficacy in primary and secondary hip fracture prevention. The Institute of Medicine recommends a daily allowance of 800 IU of Vitamin D for people 70 and over, to get to a level of serum 25-hydroxyvitamin D (25OHD) of at least 20 ng/ml (50

Calcium supplement

Health effects Bone health In healthy people, calcium supplementation is not necessary for maintaining bone mineral density, and carries risks that outweigh any benefits. Calcium intake is not significantly associated with hip fracture risk in either men or women. The U.S. Preventive Service Task Force recommends against a daily supplement of calcium or vitamin D. Although a slight increase in bone mineral density occurred in healthy children from calcium supplementation, using additional dietary calcium is not justified, according to a 2006 review. Cardiovascular impact There is good evidence that 1,000 mg to 1,500 mg of daily calcium supplementation can effect a modest reduction in blood pressure in adults who do not have a blood pressure condition.

Women's Health Initiative

CaD component findings Among the intervention cohort, a small but significant improvement in hip bone density was observed, although a significant reduction in hip fractures was not observed. However, subgroup analysis revealed a possible benefit to older women in terms of a reduced risk of hip fractures, attributable to calcium plus vitamin D supplementation. It was also found that the intervention did not have an effect on the incidence of colorectal cancer, possibly owing to the long latency associated with colorectal cancers. Calcium plus vitamin D was not found to affect the incidence of breast cancer. Finally, an increased risk of kidney stones was observed among those taking calcium plus vitamin D.

Dietary supplement

"Adequate calcium as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life." "Adequate calcium and vitamin D throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis." "Adequate calcium and vitamin D as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life." In the same year, the European Food Safety Authority also approved a dietary supplement health claim for calcium and vitamin D and the reduction of the risk of osteoporotic fractures by reducing bone loss.

Eldecalcitol

The new analogs of vitamin D, such as eldecalcitol, are observed to have stronger effects in preventing bone loss, fractures, and falls in comparison to calcitriol. Eldecalcitol is even more effective than its counterpart alfacalcidol, another vitamin D analog. Studies have shown eldecalcitol is more effective than alfacalcidol in preventing vertebral and wrist fractures, and even falls, with osteoporotic patients with vitamin D insufficiencies. Eldecalcitol is also more effective at preventing fractures than vitamin D and calcium supplements. Eldecalcitol increases calcium absorption for vitamin D deficient patients, and therefore could be used for osteoporosis treatment for all age groups.

Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60.

Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 microg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency.

The use of cholecalciferol in patients with hip fracture.

Major osteoporotic fractures are steadily increasing due to population aging. Programs of secondary prevention against refracture are essential to decrease morbidity and mortality and the cost for individuals and the society. Vitamin D supplementation and optimization of calcium intake are of a pivotal importance to start specific osteoporosis treatment and for its safety and efficacy. Cholecalciferol is the most widely employed drug for vitamin D supplementation. Aim of this study was to assess the trends in the use of vitamin D supplements containing cholecalciferol in the population of hip fracture patients older than 65 years, resident in the region of Tuscany (Italy) in the years 2011-2015 and to describe vitamin D status in a subgroup of this individuals directly referred to a bone clinic for further evaluation after hip osteoporotic fracture. Data were retrieved from the electronic anonymous regional administrative database administered by the Region of Tuscany (Italy) in the years 2011-2015 within the T.A.R.Ge.T. project (Trattamento Appropriato delle Rifratture Geriatriche in Toscana, i.e., "Appropriate treatment of geriatric refractures in Tuscany"), a program endorsed by the region itself. Data pertaining to cholecalciferol prescriptions and hospital discharge codes were retrieved and appropriately crossed to get data on the use of cholecalciferol supplements in patients before and after a hip fracture. A retrospective analysis was carried out in a subgroup of subjects (n 254) appropriately referred to the local fracture liaison service after the major osteoporotic fracture and vitamin D status in terms of serum 25(OH) vitamin D levels was assessed. The majority of subjects experiencing a hip fracture (98.2% and 88.3% in 2011 and 2015, respectively) did not receive vitamin D supplements at the time of the fracture event. Although a trend in increase in prescriptions for cholecalciferol supplements could be observed in the years of the study, the percentage of treated individuals remained low even after the fracture, since only 30-35% of subjects receives cholecalciferol supplements at one year after the fracture. Cholecalciferol remained the most prescribed drug in this population, while a substantial decrease of cholecalciferol in association with calcium salts was observed. The use of high doses of cholecalciferol has decreased in this population, while diminished the use of the drops has been accompanied by an increase in prescriptions of single monthly dose supplements. The correction of vitamin D inadequacy is preliminary to any treatment for osteoporosis and together with calcium may reduce fracture risk by itself. The prescription of vitamin D supplements is low in patients before and after a hip fracture in a Mediterranean region and despite the overall increase in vitamin use and abuse in the general population. Proper educational programs and active fracture liaison services are needed in order to bridge this gap.

Bone fracture

Other A Cochrane review of low-intensity pulsed ultrasound to speed healing in newly broken bones found insufficient evidence to justify routine use. Other reviews have found tentative evidence of benefit. It may be an alternative to surgery for established nonunions. Vitamin D supplements combined with additional calcium marginally reduces the risk of hip fractures and other types of fracture in older adults; however, vitamin D supplementation alone did not reduce the risk of fractures. Children

What is the impact of daily oral supplementation of vitamin D3 (cholecalciferol) plus calcium on the incidence of hip fracture in older people? A systematic review and meta-analysis.

Hip fractures have a huge impact in reducing the quality of life and increasing mortality. This review aims to assess the impact of daily oral supplementation of vitamin D3 plus calcium on the incidence of hip fracture in people over 65 years. PRISMA guidelines were followed and RCTs that evaluated the effectiveness of daily oral supplementation of vitamin D3 plus calcium in preventing hip fracture in adults over 65 years were included in the study. The databases such as Cochrane Library, Embase, Medline, PubMed, CINAHL, Web of Science and Scopus were searched from October 2019- January 2020.The Cochrane risk of bias tool was used to check the quality of the included studies. A meta-analysis with fixed effect model using Review Manager (Revman 5.3) was used to analyse the data. The meta-analysis of seven RCTs on vitamin D3 plus calcium supplementation and hip fracture (n = 12,620) identified odds ratio (OR) of 0.75; 95% Confidence interval (CI): 0.64, 0.87; p = .0003. Daily oral supplementation of 800 IU of Vitamin D3 plus 1200 mg of calcium was found more effective (n = 5676 participants; OR = 0.69; 95% CI: 0.58, 0.82; p < .0001) than daily oral supplementation of 800 IU of Vitamin D3 plus 1000 mg of calcium (n = 6555,OR = 1.08; 95% CI: 0.74, 1.56; p = .70) in reducing hip fracture. A meta-analysis of the seven RCTs to identify the incidence of non-vertebral fracture gave the OR of 0.80; 95% CI: 0.72, 0.89; p < .0001. A meta-analysis of three RCTs on femoral neck bone mineral density (BMD) (n = 483) gave a mean difference of 1.21; 95% CI: -0.79, 3.20; p = .24. Daily oral supplementation 800 IU of vitamin D3 plus 1200 mg of calcium reduces hip fracture and non-vertebral fracture in older people. Administering vitamin D3 and calcium supplements had no effect in increasing the femoral neck BMD. Even though it is evident from the review that optimal daily intake of vitamin D3 plus calcium supplementation help in the prevention of fracture, it is only one essential element in fracture prevention. Also, people who are on dietary supplements should be compliant with same for better result. Efforts to prevent bone loss and osteoporosis should begin from an early age. It includes maintaining a healthy lifestyle, optimal intake of calcium and vitamin D3, proper nutrition, adequate exposure to sunlight, exercise etc. Proper education on healthy lifestyle, avoiding risk factors like smoking, caffeine, alcohol and awareness of bone health should continue throughout life with emphasis during menopause when increased bone loss is expected.

Prevention of fractures in older people with calcium and vitamin D.

The greatest cause of fracture in older people is osteoporosis which contributes to increased morbidity and mortality in older people. A number of meta-analyses have been performed assessing the effectiveness of calcium supplementation alone, vitamin D supplementation alone and the combined therapy on bone loss and fracture reduction in older people. The results of these meta-analyses indicate that vitamin D supplementation alone is unlikely to reduce fracture risk, calcium supplementation alone has a modest effect in reducing total fracture risk, but compliance with calcium supplements is poor in the long term. The combination of calcium supplementation with vitamin D supplementation, particularly in those at risk of marginal and low vitamin D status reduces total fractures, including hip fractures. Therefore older people would be recommended to consume adequate dietary calcium (>1100 mg/day) together with maintaining adequate vitamin D status (>60 nmol/L 25(OH)D) to reduce risk of fracture. It is a challenge to consume sufficient dietary calcium from dietary sources, but the increasing range of calcium fortified foods could assist in increasing the dietary calcium intake of older people. In addition to the usual dairy based food sources, vitamin D supplements are likely to be required for older people with reduced mobility and access to sunlight.

Calcium, vitamin D and involutional osteoporosis.

Previous studies suggest that combined calcium and vitamin D supplementation decreases the risk of fractures in older people, particularly those living in care homes, but trials of vitamin D alone in fracture prevention have generated inconsistent results. This review examines the physiological functions of calcium and vitamin D, and the contrasting views of what constitutes an adequate dietary calcium intake and vitamin D sufficiency in adults, and highlights the results of recent large studies of calcium and vitamin D supplementation. The RECORD study shows that calcium (1000 mg/day) and vitamin D (800 IU/day), either alone or in combination, are ineffective in the secondary prevention of osteoporotic fractures in older men and women living in the community. The Northern and Yorkshire Study also suggests that calcium (1000 mg/day) and vitamin D (800 IU/day) are of no benefit in the primary prevention of fractures in community-dwelling older women. Furthermore, the Wessex study demonstrated no reduction in fractures in older people living in the community treated with annual IM injections of vitamin D (300 000 IU). The latest studies highlight that vitamin D, either alone or in combination with calcium supplementation, is ineffective in the primary or secondary prevention of fractures in community-dwelling older people. In contrast, calcium and vitamin D supplementation prevents fractures in institutionalized elderly people, who commonly have vitamin D deficiency and secondary hyperparathyroidism.

A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study.

survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture. There is little consensus about secondary prevention. Many are given calcium and vitamin D, but the evidence supporting this is circumstantial. to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers, bone mineral density and rate of falls in elderly women post-hip fracture. randomised controlled trial. orthogeriatric rehabilitation ward. 150 previously independent elderly women, recruited following surgery for hip fracture, were assigned to receive a single injection of 300,000 units of vitamin D(2), injected vitamin D(2) plus 1 g/day oral calcium, 800 units/day oral vitamin D(3) plus 1 g/day calcium, or no treatment. Follow-up was one year, with measurement of 25-hydroxyvitamin D, parathyroid hormone, bone mineral density, and falls. mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups, more so in the group receiving combined oral vitamin D and calcium. Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later. Bone mineral density showed small but statistically significant differences of up to 4.6% between actively treated groups and placebo. Relative risk of falling in the groups supplemented with vitamin D was 0.48 (95% CI 0.26-0.90) compared with controls. Vitamin D supplementation, either orally or with injected vitamin D, suppresses parathyroid hormone, increases bone mineral density and reduces falls. Effects may be more marked with calcium co-supplementation. The 300,000 units of injected vitamin D may not last a whole year.

Calcium and vitamin d in the prevention and treatment of osteoporosis.

An increasing prevalence of calcium and/or vitamin D deficiency in the general population (especially, but not only, in elderly subjects) has been emphasized in recent epidemiologic studies. These deficiencies could be responsible for accelerated bone loss mediated by secondary hyperpara-thyroidism and increased bone turnover and could explain the dramatic increase of the incidence of osteoporotic fractures with age. High calcium intake in prepubertal girls seems to be associated with higher peak bone mass in late adolescence. Calcium supplementation could slow bone turnover and bone loss in particular subsets of patients, including calcium-deficient postmenopausal women and elderly patients. A specific antif-racture effect of calcium supplementation in postmenopausal osteoporotic patients has not been established, but a calcium-plus-low-dose-vitamin D3 supplementation has been suggested to decrease the peripheral fracture incidence (especially hip fracture) in elderly institutionalized women. After a critical review of these data, some practical recommendations are suggested.

Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials.

Antifracture efficacy with supplemental vitamin D has been questioned by recent trials. We performed a meta-analysis on the efficacy of oral supplemental vitamin D in preventing nonvertebral and hip fractures among older individuals (> or =65 years). We included 12 double-blind randomized controlled trials (RCTs) for nonvertebral fractures (n = 42 279) and 8 RCTs for hip fractures (n = 40 886) comparing oral vitamin D, with or without calcium, with calcium or placebo. To incorporate adherence to treatment, we multiplied the dose by the percentage of adherence to estimate the mean received dose (dose x adherence) for each trial. The pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) for prevention of nonvertebral fractures and 0.91 (95% CI, 0.78-1.05) for the prevention of hip fractures, but with significant heterogeneity for both end points. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI, 0.72-0.89; n = 33 265 subjects from 9 trials) for nonvertebral fractures and 0.82 (95% CI, 0.69-0.97; n = 31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in community-dwelling individuals (-29%) and institutionalized older individuals (-15%), and its effect was independent of additional calcium supplementation. Nonvertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.


The correct answer is: 4. Antihypertensive. In particular, hydrochlorothiazide, as a thiazide, is primarily responsible for this patient's hypokalemia.

The [HIDDEN] Antihypertensive. In particular, hydrochlorothiazide, as a thiazide, is primarily responsible for this patient's hypokalemia.

A 60-year-old woman diagnosed with chronic bronchopathy, diabetes mellitus, hypertension and treated for 4 months with Omeprazole, Metformin, Salbutamol, Ipratropium Bromide and Enalapril 20 mg + Hydrochlorothiazide 25 mg comes to your office for fatigue, decreased appetite, with slight dyspnea and occasional cough, variable stools, sometimes soft and without urinary symptoms. Blood tests show leukocytes 10,000/mm³, Ht 35%, MCV 80, Glucose 150 mg/dl, Urea 80 mg/dl, Creatinine 1.6 mg/dl, Sodium 133 mEq/l and Potassium 2.9 mEq/l. What is the most likely cause of hypokalemia?

[Metformin and Diabetes: still has a sense of its use in patients CKD stage II or is an additional risk factor?]

Pz woman of 62 years comes to P.S.G. for fatigue, low-grade fever, diuresis present. A history of hypertension refers to therapy for about five years, diabetes mellitus for about two years in therapy with Metformin 1gr x 3 gg / day. Blood tests: BUN 195 mg / dL, creatinine 8.0 mg / dl, Ph 6877, HCO3 5.1 mmol / L BE -29.1 mmol / l. Rapid clinical deterioration with occurrence of arterial hypotension - 85/60 mmHg, stupor. Start therapy Bicarbonates ev, is positioned in Urgency CVC and it undergoes AFB with infusion of bicarbonates 2000 ml / h for 4 hours, blood flow rate 250 ml / min., the hemodynamics has been supported with dopamine infusion 200 mg: 2 vials in 250 cc of physiological vel 30 - 40 ml / h, The pc after undergoing three AFB, interrupted the dialysis for resumption of diuresis spontaneous and progressive improvement of renal function and blood pressure. Monitored, after discharge, the parameters of renal function decreased to within normal limits, clearance compatible with IRC II - III stage. dehydration, fever, IRC II stadium, undiagnosed caused, in a very short time, an accumulation of metformin, which has been the cause of metabolic acidosis. The pc. saved thanks to the positioning of the CVC and to the AFB in the treatment with the infusion of large quantities of Bicarbonates e.v. The use of metformin in pcs. > 50 years and / or creatinine clearance <60 ml / min., must be subordinated to the preliminary study and periodic renal function.

[Non-fatal hyperkalemia in lactic acidosis due to metformin overdose. Report of one case].

We report a 74-year-old man with diabetes mellitus type 2 and hypertension, who recently underwent coronary bypass surgery due to severe triple vessel disease receiving cardiological and combined antidiabetic therapy, including metformin 4 g/day. He was admitted with abdominal pain, nausea, vomiting, diarrhea and loss of consciousness. At admission, he was disoriented and agitated with signs of poor perfusion. His blood pressure was 80/70 mmHg, pulse rate 40 beats/min, respiratory rate 20-breaths/min, and axillary temperature 35 °C. Biochemical profile revealed an extreme hyperkalemia of 15.4 mEq/L (double checked), elevated creatinine, uremia and brain natriuretic peptide; hypoglycemia (blood glucose 68 mg/dl) and normal C Reactive Protein. Arterial blood gases revealed severe lactic acidemia. The electrocardiogram showed sinus bradycardia, simple AV block, widened QRS with prominent T wave and prolonged QT. He was admitted to the Intensive Care Unit (ICU) with the suspicion of lactic acidosis associated with metformin, receiving fluid management, intravenous hypertonic glucose plus insulin and sodium bicarbonate, mechanical ventilation, vasopressor therapy, a temporary pacemaker lead, in addition to continuous venovenous hemodiafiltration. Two days later, the patient experienced a significant clinical improvement with normalization of the acid-base status, plasma lactate and potassium levels. On day 9, diuresis was recovered, creatinine and uremia returned to normal levels and the patient was discharged from the ICU.

Ranolazine Induced Bradycardia, Renal Failure, and Hyperkalemia: A BRASH Syndrome Variant.

Ranolazine is a well-known antianginal drug, that was first licensed for use in the United States in 2006. It was objectively shown to improve exercise capacity and to lengthen the time to symptom onset in patients with coronary artery disease. The most commonly reported side effects of ranolazine include dizziness, headache, constipation, and nausea. Here, we describe a case of bradycardia, hyperkalemia, and acute renal injury in the setting of ranolazine use. Our patient is an 88-year-old female who presented with abdominal pain, nausea, and vomiting. Her medical comorbidities included hypertension, diabetes, CAD, heart failure with preserved ejection fraction, paroxysmal atrial fibrillation, hypothyroidism, and a history of cerebrovascular accident without any residual deficits. Her prescription regimen included amlodipine, furosemide, isosorbide mononitrate, levothyroxine, metformin, omeprazole, and ranolazine. Physical examination was remarkable for bradycardia and decreased breath sounds in the left lower lung field. Laboratory studies were significant for a serum potassium level of 6.8 mEq/L and a serum creatinine level of 1.6 mg/dL. She was given insulin with dextrose, sodium polystyrene, and calcium gluconate in addition to fluids. Her bradycardia and renal function worsened over the next 24 hours. Ranolazine was discontinued. Metabolic derangements were treated appropriately. After 48 hours from presentation, potassium and renal function returned to baseline and her heart rate improved to a range of 60-100 bpm. She was discharged with an outpatient cardiology follow-up. Ranolazine treatment was not continued upon discharge. In summary, our case illustrates an association between ranolazine and renal failure induced hyperkalemia, leading to conduction delays in the myocardium. Though further studies are warranted, we suspect that this is a variant of the recently described BRASH syndrome. We propose that in cases such as ours, along with treatment of the hyperkalemia, medication review and removal of any offending agent should be considered.

Metformin-associated lactic acidosis treated with continuous renal replacement therapy.

Lactic acidosis is an infrequent complication of metformin therapy for diabetes mellitus. The presence of clinical conditions, such as renal failure, increases the risk of metformin-associated lactic acidosis (MALA). We present a case of lactic acidosis in a patient with diabetes treated with metformin, complicated by acute renal failure in preexisting chronic nephropathy. A 70-year-old white male, weighing 77 kg, with diabetes mellitus, coronary heart disease, congestive heart failure (New York Heart Association class III), moderate essential hypertension (stage 2), and renal dysfunction (serum urea, 90 mg/dL; serum creatinine, 1.5 mg/dL; creatinine clearance, 49.8 mL/min/1.73 m2) presented to the emergency department of the General Hospital of Rhodes (Rhodes, Greece), complaining of malaise, respiratory distress, myalgias, disorientation, abdominal discomfort, and increasing somnolence of insidious onset. The patient's regimen included isosorbide mononitrate 60 mg QD, furosemide 40 mg QD, quinapril 20 mg QD, and metformin 850 mg TID. Before this hospitalization, he had received a 2-week course of oral diclofenac sodium 25 mg TID for low back pain. Preliminary laboratory evaluation found leukocytosis (27,300/mm3), severe renal failure (serum urea, 215 mg/dL; serum creatinine, 7.4 mg/dL; calculated creatinine clearance, 10.1 mL/min/1.73 m2), and a high anion gap metabolic acidosis (pH, 6.95; anion gap, 33 mEq/L) in arterial blood gas analysis. His medical and drug history, the clinical and laboratory findings, and the determination of lactate in samples of plasma (7.8 mEq/L), aroused the suspicion of MALA. The Naranjo algorithm scores for metformin and diclofenac sodium were 6 and 7, respectively. The patient received a single session of bicarbonate-buffered continuous venovenous hemodiafiltration (CWHDF) that lasted 16 hours. Ultimately, he was stabilized, and progressive restoration of acid-base balance and renal function was observed. We suspect that lactic acidosis may have been related to the use of metformin, the presence of heart and renal failure (contributing to metformin toxicity), and previous use of diclofenac sodium. CVVHDF has an advantage over conventional intermittent hemodialysis in that it corrects acidosis and removes lactate and metformin without risk of hypernatremia or fluid overload. MALA should be strongly suspected in diabetic patients presenting with high anion gap metabolic acidosis and increased serum lactate level. In the case described, prompt recognition of lactic acidosis and early application of bicarbonate-buffered CVVHDF produced successful results.

Ventricular fibrillation as the first manifestation of primary hyperaldosteronism.

50 years old female patient, with history of diabetes mellitus and hypertension, receiving metformin (500 mg BID) and atenolol (50 mg BID), presented to the Emergency Room with asthenia and dizziness. The patient was also receiving alternative medication (Dragon Blanco) which contains no licorice. During the emergency workup she developed syncope and three episodes of ventricular fibrillation. She was electrically defibrillated and treated with amiodarone and potassium replacement. The patient was admitted to the Intensive Care Unit. Physical exam: BP: 160/90 mm Hg, RR: 15, Pulse: 83: Cardiovascular: grade II systolic murmur which irradiated to the neck. The rest of the examination was unremarkable. Labs: Na: 138 meg/dl, K: 1.6 meg/dl, Cl: 84 meg/dl, BUN: 17 mg/dl, Creat.: 1.1 mg/dl, Gluc.: 148 mg/dl, Renin: < 0.15 mcgr/ml, Aldosterone: 20.1 mcg%. Aldosterone-Renin ratio: 133. Chest X-Ray: cardiomegaly. EKG: RBBB, long QT segment and prominent broad "u" waves compatible with severe hypokalemia. A CT SCAN of the Abdomen/Pelvis showed a 3.2 cm right adrenal mass, most likely adenomatous. The patient was discharged with the diagnosis of primary aldosteronism. Due to the diagnosis of diabetes mellitus, hypertension and the three episodes of ventricular fibrillation, surgical treatment was postponed until stress tests and eventual coronary angiographic studies were performed. We found in our review of the medical literature 9 reports of fibrillation associated with hyperaldosteronism. Of those, only two were associated with primary aldosteronism, one of them with a fatal outcome. This case is highly unusual and emphasizes the importance of an adequate diagnosis of secondary hypertension.

A probable case of gabapentin-related reversible hearing loss in a patient with acute renal failure.

As described in the literature, gabapentin toxicity in patients with impaired renal function can manifest as coma, myoclonus, tremulousness, or altered mental status. Gabapentin is an antiepileptic agent indicated for use as an adjunct therapy in partial seizures and postherpetic neuralgia but is also prescribed for the treatment of diabetic peripheral neuropathy. A 46-year-old white woman (height, 167 cm; weight, 177 kg; body mass index, 62.8 kg/m2) with a 6-year history of diabetes mellitus and previously normal renal function, presented to the emergency department of Wake Forest University Baptist Medical Center with anuria (a serum creatinine level of 7.4 mg/dL), hearing loss, myoclonus, and confusion with hallucinations lasting for 3 days. Her blood pressure was 110/74 mm Hg. The patient's preadmit medication list included: lisinopril (40 mg QD), hydrochlorothiazide (25 mg QD), and furosemide (80 mg QD) for hypertension; atorvastatin (10 mg QD) for hyperlipidemia; omeprazole (20 mg QD) for gastroesophageal reflux disease; salmeterol/fluticasone inhaler (100/50 microg; 1 puff BID) and albuterol metered-dose inhaler (90 microg as needed) for asthma; metformin (500 mg BID) and insulin lispro per sliding scale for type 2 diabetes mellitus; oxycodone controlled release (60 mg TID) for chronic osteoarthritis and low back pain; alprazolam (0.5 mg every 8 hours as needed) for generalized anxiety disorder; venlafaxine (150 mg BID) for depression; and gabapentin (300 mg TID) for diabetic peripheral neuropathy. The patient's symptoms (hearing loss, myoclonus, and confusion) improved after 1 session of hemodialysis (approximately 10 hours following admission) and had resolved at the time of discharge (4 days later). On admission, the gabapentin concentration was 17.6 microg/mL, and following hemodialysis, the gabapentin concentration was undetectable (by discharge/day 4). The timing of the patient's last dose of gabapentin is unknown. Normal doses for the treatment of diabetic peripheral neuropathy range from 900 to 3600 mg/d divided 3 times daily. We report a patient with acute renal failure who developed hearing loss, myoclonus, and confusion with hallucinations in the presence of elevated gabapentin concentrations. Due to rapid improvement after hemodialysis and discontinuation of gabapentin, we believe that these symptoms were probably due to gabapentin toxicity.

Pharmacology_Katzung

Ramin Sam, MD, Harlan E. Ives, MD, PhD, & David Pearce, MD A 65-year-old man has a history of diabetes and chronic kidney disease with baseline creatinine of 2.2 mg/dL. Despite five different antihypertensive drugs, his clinic blood pres-sure is 176/92 mm Hg; he has mild dyspnea on exertion and 2–3+ edema on exam. He has been taking furosemide 80 mg twice a day for 1 year now. At the clinic visit, hydrochlorothi-azide 25 mg daily is added for better blood pressure control and also to treat symptoms and signs of fluid overload. Two weeks later, the patient presents to the emergency depart-ment with symptoms of weakness, anorexia, and generalized malaise. His blood pressure is now 91/58 mm Hg, and he has lost 15 kg in 2 weeks. His laboratory tests are signifi-cant for a serum creatinine of 10.8 mg/dL. What has led to the acute kidney injury? What is the reason for the weight loss? What precautions could have been taken to avoid this hospitalization?

InternalMed_Harrison

Na+ 120 K+ 4.3 Cl− 89 HCO3− 23 BUN 8 Creat 1.0 Glu 93 Alb 3.1 Ca 8.9 Phos 2.8 Mg 2.0 Plasma osm 248 mOsm/kg Cortisol 25 μg/dL TSH 2.6 Uric acid 2.7 mg/dL Urine: Na+ 97 K+ 22 Cl− 86 Osm 597 The patient was treated with furosemide, 20 mg PO bid, and salt tablets. The plasma Na+ concentration increased to 129 meq/L with this therapy; however, the patient developed orthostatic hypotension and dizziness. He was started on demeclocycline, 600 mg PO in the morning and 300 mg in the evening, just before discharge from hospital. Plasma Na+ concentration increased to 140 meq/L with a BUN of 23 and creatinine of 1.4, at which point demeclocycline was reduced to 300 mg PO bid. Bronchoscopic biopsy eventually showed small-cell lung cancer; the patient declined chemotherapy and was admitted to hospice. What factors contributed to this patient’s hyponatremia? What are the therapeutic options?

Co-amilozide

Co-amilozide (BAN) is a non-proprietary combination of amiloride and hydrochlorothiazide. Co-amilozide is used in the treatment of hypertension and congestive heart failure with the tendency of the thiazide to cause low potassium levels (hypokalaemia) offset by the potassium-sparing effects of amiloride. Formulation Two strengths of co-amilozide are currently available in the UK: 2.5 mg amiloride and 25 mg hydrochlorothiazide, BAN of Co-amilozide 2.5/25 (brand name Moduret 25) 5 mg amiloride and 50 mg hydrochlorothiazide, BAN of Co-amilozide 5/50 (brand name Moduretic) In North America: Moduretic (U.S., Canada) Moduretic 5-50 (U.S., Canada) Novamilor (Canada) Side effects The most common side effect is headache (about 8% of people taking it) and nausea, loss of appetite, weakness, rash and dizziness (each about 3%).

InternalMed_Harrison

Fluid and Electrolyte Imbalances and Acid-Base Disturbances: Case Examples David B. Mount, Thomas D. DuBose, Jr. CASE 1 64e A 23-year-old woman was admitted with a 3-day history of fever, cough productive of blood-tinged sputum, confusion, and orthostasis. Past medical history included type 1 diabetes mellitus. A physical examination in the emergency department indicated postural hypo-tension, tachycardia, and Kussmaul respiration. The breath was noted to smell of “acetone.” Examination of the thorax suggested consolidation in the right lower lobe. Sodium 130 meq/L Potassium 5.0 meq/L Chloride 96 meq/L CO2 14 meq/L Blood urea nitrogen (BUN) 20 mg/dL Creatinine 1.3 mg/dL Glucose 450 mg/dL Pneumonic infiltrate, right lower lobe The diagnosis of the acid-base disorder should proceed in a stepwise fashion: 1. The normal anion gap (AG) is 8–10 meq/L, but in this case, the AG is elevated (20 meq/L). Therefore, the change in AG (ΔAG) = ~10 meq/L. 2.

Case Study: 60-Year-Old Female Presenting With Shortness of Breath -- Case Presentation

Her current medications include fluticasone-vilanterol 100-25 mcg inhaled daily, hydralazine 50 mg by mouth, 3 times per day, hydrochlorothiazide 25 mg by mouth daily, albuterol-ipratropium inhaled every 4 hours PRN, levothyroxine 175 mcg by mouth daily, metformin 500 mg by mouth twice per day, nebivolol 5 mg by mouth daily, aspirin 81 mg by mouth daily, vitamin D3 1000 units by mouth daily, clopidogrel 75 mg by mouth daily, isosorbide mononitrate 60 mg by mouth daily, and rosuvastatin 40 mg by mouth daily.

Spironolactone

It is recommended that alternatives to spironolactone be considered if serum creatinine is greater than 2.5 mg/dL (221 μmol/L) in males or greater than 2 mg/dL (176.8 μmol/L) in females, if glomerular filtration rate is below 30 mL/min or with a serum potassium of greater than 5.0 mEq/L given the potential for adverse events detailed elsewhere in this article. Doses should be adjusted according to the degree of kidney function as well.

Metformin-induced lactic acidosis in a type 2 diabetic patient with acute renal failure.

Metformin is a biguanide commonly used in type 2 diabetes mellitus (DM). Lactic acidosis, a potentially life-threatening metabolic disorder, may be due to a number of different causes, including metformin therapy. We present a case of a severe metformin-induced lactic acidosis in a patient with type 2 DM, admitted to the emergency department with a history of dehydration due to diarrhoea and complicated by acute renal failure. Patient complained malaise and severe weakness and was tachypneic (Kussmaul's respiration), agitated and confused, with a Glasgow Coma Scale score of 13/15. Heart rate was 75 b/min and blood pressure 110/80 mmHg. The pH was 6.87, HCO3- 3 mmol/l, lactate 15 mmol/l, potassium 6.9 mEq/l. The renal function was markedly impaired with a creatinine of 9.75 mg/dl, and pancreatic enzymes, amylase and lipase, were also increased in absence of abdominal pain. Patient was treated with intravenous fluids, bicarbonate infusion and haemodialysis with bicarbonate buffered replacement fluid. Clinical conditions improved rapidly, with a progressive normalization of the acid-base balance and the other laboratory data. Authors discuss the pathophysiologic mechanisms of these alterations with particular regard to the role played by metformin as potential cause of lactic acidosis.

InternalMed_Harrison

A 78-year-old man was admitted with pneumonia and hyponatremia. Plasma Na+ concentration was initially 129 meq/L, decreasing within 3 days to 118–120 meq/L despite fluid restriction to 1 L/d. A chest computed tomography (CT) revealed a right 2.8 × 1.6 cm infrahilar mass and postobstructive pneumonia. The patient was an active smoker. Past medical history was notable for laryngeal carcinoma treated 15 years prior with radiation therapy, renal cell carcinoma, peripheral vascular disease, and hypothyroidism. On review of systems, he denied headache, nausea, and vomiting. He had chronic hip pain, managed with acetaminophen with codeine. Other medications included cilostazol, amoxicillin/clavulanate, digoxin, diltiazem, and thyroxine. He was euvolemic on examination, with no lymphadenopathy and a normal chest examination. Na+ 120 K+ 4.3 Cl− 89 HCO3− 23 BUN 8 Creat 1.0 Glu 93 Alb 3.1 Ca 8.9 Phos 2.8 Mg 2.0 Plasma osm 248 mOsm/kg Cortisol 25 μg/dL TSH 2.6 Uric acid 2.7 mg/dL

Ranson criteria

Acute pancreatitis not secondary to gallstones At admission: Blood glucose > 11.11 mmol/L (> 200 mg/dL) Age > 55 years Serum LDH > 350 IU/L Serum AST > 250 IU/L WBC count > 16000 cells/mm3 Within 48 hours: Serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit decreased by > 10% Oxygen (hypoxemia with PaO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 4 mEq/L Sequestration of fluids > 6 L Acute pancreatitis secondary to gallstones At admission: Glucose > 220 mg/dl Age > 70 years LDH > 400 IU/L AST > 250 IU/ 100 ml WBC count > 18000 cells/mm3 Within 48 hours: Serum calcium < 8 mg/dL Hematocrit decreased by > 10% Base deficit > 4 mEq/L BUN increased by > 2 mg/dL Sequestered fluid > 6L

Metabolic syndrome

EGIR The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following: Central obesity: waist circumference ≥ 94 cm or 37 inches (male), ≥ 80 cm or 31.5 inches (female) Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia Blood pressure ≥ 140/90 mmHg or antihypertensive medication Fasting plasma glucose ≥ 6.1 mmol/L NCEP The U.S. National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following: Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female) Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dl) Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female) Blood pressure ≥ 130/85 mmHg (or treated for hypertension) Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl)

[A case of lactic acidosis caused by buformin in an oldest elderly diabetic patient].

A 93-year-old male was urgently admitted to our hospital with dyspnea and disturbance of consciousness. The patient had been visiting a general physician regularly for ten years, for treatment of type 2 diabetes. He had been treated with glibenclamide and voglibose, until voglibose was replaced with buformin 3 months before admission. During pre-admission treatment, his HbA1c was 10-12% and serum Cr level was around 2mg/dL, but insulin therapy had never been considered because of "being too old". The patient had started taking furosemide one year before admission, because of edema of the lower legs, and also spironolactone two months before admission. Anorexia had continued for one month before admission on May 29, 2003. On admission, his laboratory data were; blood glucose 87mg/dL, HbA1c 12.5%, BUN 75mg/dL, Cr 3.9mg/dL, lactate 253.1 mg/dL, and blood gas analysis; pH 6.97, anion gap 45.3mmol/L breathing room air, suggesting marked lactic acidosis with renal failure. Intensive care with bicarbonate and fluid therapy was successful, and his glycemic control improved markedly with insulin. On the other hand, his activity of daily living (ADL) severely deteriorated while in hospital Home follow-up was therefore not indicated, and he had to change a hospital for further follow-up. This case report gives rise to the question of how we should manage diabetes in the oldest elderly, including the use of insulin and biguanides. In addition, complications of biguanides in the elderly are reviewed.

[A patient with severe hyperkalaemia -- an emergency after RALES].

A 59-year-old man was referred to the hospital for psychiatric reasons. To control hypertension and chronic heart failure he had been treated with 5 mg ramipril and 12.5 mg hydrochlorothiazide. In addition, he received 25 mg spironolactone. A prostate disease was diagnosed two months ago. Laboratory analysis revealed a severe hyperkalemia (9.3 mmol/l) as well as an increase in creatinine (24.3 mg/dl) and urea nitrogen (349.0 mg/dl). The ECG showed a bradycardia with increased T-wave amplitudes. Abdominal sonography revealed a full urinary bladder. Administration of terbutaline, sodium bicarbonate, and glucoseinfusion lowered potassium level to 6.3 mmol/l before hemodialysis was started. Hyperplasia of the prostate gland was found to be the reason for acute renal failure. Dialysis treatment was only temporarily necessary; afterwards, the patient was transferred to the urology department for subsequent therapy. Hyperkalemia is a life-threatening emergency that requires immediate therapy. Conservative treatment allows to partially correct water-electrolyte imbalance until hemodialysis can be performed. Hyperkalemia often results from the administration of combination therapy with ACE-inhibitors/AT (1)-antaganonists and antikaliuretic diuretics (spironolactone) in renal failure.

Metabolic syndrome

IDF The International Diabetes Federation consensus worldwide definition of metabolic syndrome (2006) is: Central obesity (defined as waist circumference# with ethnicity-specific values) AND any two of the following: Raised triglycerides: > 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality Reduced HDL cholesterol: < 40 mg/dL (1.03 mmol/L) in males, < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality Raised blood pressure (BP): systolic BP > 130 or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension Raised fasting plasma glucose (FPG): >100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes If FPG is >5.6 mmol/L or 100 mg/dL, an oral glucose tolerance test is strongly recommended, but is not necessary to define presence of the syndrome. # If BMI is >30 kg/m2, central obesity can be assumed and waist circumference does not need to be measured

Tumor lysis syndrome

Cairo-Bishop definition In 2004, Cairo and Bishop defined a classification system for tumor lysis syndrome. Laboratory tumor lysis syndrome: abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy. uric acid > 8 mg/dL or 25% increase potassium > 6 meq/L or 25% increase phosphate > 4.5 mg/dL or 25% increase calcium < 7 mg/dL or 25% decrease Clinical tumor lysis syndrome: laboratory tumor lysis syndrome plus one or more of the following: increased serum creatinine (1.5 times upper limit of normal) cardiac arrhythmia or sudden death seizure A grading scale (0–5) is used depending on the presence of lab TLS, serum creatinine, arrhythmias, or seizures.

Hyperglycemia

Scientific journals are moving towards using mmol/l; some journals now use mmol/l as the primary unit but quote mg/dl in parentheses. Glucose levels vary before and after meals, and at various times of day; the definition of "normal" varies among medical professionals. In general, the normal range for most people (fasting adults) is about 4 to 6 mmol/l or 80 to 110 mg/dl. (where 4 mmol/l or 80 mg/dl is "optimal".) A subject with a consistent range above 7 mmol/l or 126 mg/dl is generally held to have hyperglycemia, whereas a consistent range below 4 mmol/l or 70 mg/dl is considered hypoglycemic. In fasting adults, blood plasma glucose should not exceed 7 mmol/l or 126 mg/dL. Sustained higher levels of blood sugar cause damage to the blood vessels and to the organs they supply, leading to the complications of diabetes.

InternalMed_Harrison

Diagnostic Approach The cause of hypokalemia is usually evident from history, physical examination, and/or basic laboratory tests. The history should focus on medications (e.g., laxatives, diuretics, antibiotics), diet and dietary habits (e.g., licorice), and/or symptoms that suggest a particular cause (e.g., periodic weakness, diarrhea). The physical examination should pay particular attention to blood pressure, volume status, and signs suggestive of specific hypokalemic disorders, e.g., hyperthyroidism and Cushing’s syndrome. Initial laboratory evaluation should include electrolytes, BUN, creatinine, serum osmolality, Mg2+, Ca2+, a complete blood count, and urinary pH, osmolality, creatinine, and electrolytes (Fig. 63-7). The presence of a non–anion gap acidosis suggests a distal, hypokalemic renal tubular acidosis or diarrhea; calculation of the urinary anion gap can help differentiate these two diagnoses. Renal K+ excretion can be assessed with a 24-h urine collection; a 24-h K+

Diabetes

Diagnosis Diabetes mellitus is diagnosed with a test for the glucose content in the blood, and is diagnosed by demonstrating any one of the following: Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL). For this test, blood is taken after a period of fasting, i.e. in the morning before breakfast, after the patient had sufficient time to fast overnight. Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 gram oral glucose load as in a glucose tolerance test (OGTT) Symptoms of high blood sugar and plasma glucose ≥ 11.1 mmol/L (200 mg/dL) either while fasting or not fasting Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).

[A trichlormethiazide-amiloride combination in essential hypertension].

Following a placebo period of 2 weeks 39 patients with essential hypertension were given during 4 weeks a combination of 2 mg trichlormethiazide and 2 mg amiloride (Esmalorid). If the blood pressure was adequately reduced treatment was continued for a further 4 weeks; if not, a double dose was dispensed during the second 4-week period. Patients with a diastolic blood pressure under 90 mm Hg after 8 weeks when treated with a 1 mg dose, were subsequently treated with a 1 mg dose for a period of 3 months. After 8 weeks of treatment mean systolic blood pressure was reduced from 167 +/- 17 mm Hg to 151 +/- 19 mm Hg (sitting) and from 163 +/- 15 mm Hg to 148 +/- 18 mm Hg (standing), while mean diastolic blood pressure was decreased from 104 +/- 6 mm Hg to 93 +/- 8 mm Hg (sitting) and from 105 +/- 6 mm Hg to 94 +/- 8 mm Hg (standing). In 29 patients diastolic blood pressure had dropped to values under 95 mm Hg. Serum potassium remained constant during the treatment except for three patients with values outside the normal range (3.3, 3.4 and 5.2 mmol/l). The other serum electrolytes, glucose, creatinine, blood lipids, transaminases, hemogram, as well as body weight and heart rate remained unchanged. Two patients complained of side effects and did not complete the study. All other patients tolerated the treatment well.

Magnesium deficiency

Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in multiple symptoms. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, and nystagmus. Complications may include seizures or cardiac arrest such as from torsade de pointes. Those with low magnesium often have low potassium. Causes include low dietary intake, alcoholism, diarrhea, increased urinary loss, poor absorption from the intestines, and diabetes mellitus. A number of medications may also cause low magnesium, including proton pump inhibitors (PPIs) and furosemide. The diagnosis is typically based on finding low blood magnesium levels (hypomagnesemia). Normal magnesium levels are between 0.6 and 1.1 mmol/L (1.46–2.68 mg/dL) with levels less than 0.6 mmol/L (1.46 mg/dL) defining hypomagnesemia. Specific electrocardiogram (ECG) changes may be seen.

Amiloride -- Adverse Effects

Amiloride has an FDA-boxed warning for hyperkalemia, either alone or even when combined with hydrochlorothiazide. [19] Hyperkalemia might be fatal, especially in people with diabetes mellitus, elderly patients, and patients with renal impairment. Hyperkalemia tends to occur in patients not receiving a concomitant kaliuretic diuretic. When amiloride is used concomitantly with thiazides, the risk of hyperkalemia drops to 1 to 2%. Other Adverse Effects [20] Central nervous system: headache, fatigue, and dizziness Musculoskeletal system: muscle cramps and weakness Gastrointestinal system: nausea, vomiting, diarrhea/constipation, abdominal pain, and anorexia Endocrine and metabolic: glucose intolerance, hyperuricemia as a side effect of all potassium-sparing diuretics including amiloride, hyperchloremic metabolic acidosis, hyponatremia, and gynecomastia. Respiratory: dyspnea and cough Genitourinary: impotence

Type 2 diabetes

fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl) or with a glucose tolerance test, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/dl) A random blood sugar of greater than 11.1 mmol/l (200 mg/dl) in association with typical symptoms or a glycated hemoglobin (HbA1c) of ≥ 48 mmol/mol (≥ 6.5 DCCT %) is another method of diagnosing diabetes. In 2009 an International Expert Committee that included representatives of the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the European Association for the Study of Diabetes (EASD) recommended that a threshold of ≥ 48 mmol/mol (≥ 6.5 DCCT %) should be used to diagnose diabetes. This recommendation was adopted by the American Diabetes Association in 2010. Positive tests should be repeated unless the person presents with typical symptoms and blood sugars >11.1 mmol/l (>200 mg/dl).

Extreme hyperkalaemia caused by concomitant use of a NSAID and an ace inhibitor in an elderly patient.

Extreme hyperkalaemia is a life-threatening electrolyte disorder. It is relatively common in patients with severe renal insufficiency. This report describes a case of extreme hyperkalaemia caused by drugs in an 82-year-old female patient without severe renal insufficiency, who was successfully treated without haemodialysis. The patient had been treated for arterial hypertension and type 2 diabetes mellitus for 30 years. Over the last years she had been receiving enalapril and metformin. Three weeks before the admission to the hospital, she was receiving a non-steroidal anti-inflammatory drug (NSAID) because of the back pain. She was admitted to hospital due to a collapse and weakness in the limbs. Laboratory tests showed extreme hyperkalaemia, high blood sugar, metabolic acidosis, elevated serum creatinine and blood urea nitrogen (BUN), and a slightly elevated serum sodium. On ECG, we noticed typical signs of hyperkalaemia.The patient was treated with a slow intravenous bolus of calcium gluconate and intravenous infusion of sodium chloride with insulin, glucose with insulin and sodium bicarbonte. After the treatment, all laboratory findings normalised together and the patient felt better. This case shows that physicians should be very careful when prescribing NSAIDs to elderly patients treated with drugs that affect renal function.

InternalMed_Harrison

A 63-year-old man was admitted to the intensive care unit (ICU) with a severe aspiration pneumonia. Past medical history included schizophrenia, for which he required institutional care; treatment had included neuroleptics and intermittent lithium, the latter restarted 6 months before admission. The patient was treated with antibiotics and intubated for several days, with the development of polyuria (3–5 L/d), hypernatremia, and acute renal insufficiency; the peak plasma Na+ concentration was 156 meq/L, and peak creatinine was 2.6 mg/dL. Urine osmolality was measured once and reported as 157 mOsm/kg, with a coincident plasma osmolality of 318 mOsm/kg. Lithium was stopped on admission to the ICU. On physical examination, the patient was alert, extubated, and thirsty. Weight was 97.5 kg. Urine output for the previous 24 h had been 3.4 L, with an IV intake of 2 L/d of D5W.

InternalMed_Harrison

Diuretics Thiazides Hydrochlorothiazide 6.25–50 mg (1–2) Diabetes, dyslipidemia, hyperuricemia, gout, hypokalemia Chlorthalidone 25–50 mg (1) Loop diuretics Furosemide 40–80 mg (2–3) CHF due to systolic dysfunc-Diabetes, dyslipidemia, hypertion, renal failure uricemia, gout, hypokalemia Aldosterone antagonists Spironolactone 25–100 mg (1–2) CHF due to systolic dysfunc-Renal failure, hyperkalemia tion, primary aldosteronism Renal failure, hyperkalemia Triamterene 50–100 mg (1–2) Beta blockers Asthma, COPD, 2ndor 3rd-degree heart block, sick- Cardioselective Atenolol 25–100 mg (1) Angina, CHF due to systolic sinus syndrome dysfunction, post-MI, sinus tachycardia, ventricular tachyarrhythmias Metoprolol 25–100 mg (1–2) Nonselective Propranolol 40–160 mg (2) Propranolol LA 60–180 (1) Combined alpha/beta Labetalol 200–800 mg (2) ?Post-MI, CHF Carvedilol 12.5–50 mg (2) Alpha antagonists

Hyperglycemia

Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/l (200 mg/dL), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/l (~250–300 mg/dL). A subject with a consistent range between ~5.6 and ~7 mmol/l (100–126 mg/dL) (American Diabetes Association guidelines) is considered slightly hyperglycemic, and above 7 mmol/l (126 mg/dL) is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.

Co-amilozide

Side effects The most common side effect is headache (about 8% of people taking it) and nausea, loss of appetite, weakness, rash and dizziness (each about 3%). Common side effects (1/10 - 1/100) include: General: weakness, fatigue, loss of appetite, headache, dizziness. Circulatory system: arrhythmia. Gastrointestinal: nausea, diarrhea, abdominal pain. Skin: exanthema, itching. Respiratory system: shortness of breath, cough. Metabolic: elevated blood sugar in diabetic patients, elevated uric acid levels in the blood. Musculoskeletal: pain in the limbs. References Potassium-sparing diuretics Thiazides Combination drugs