The presence of inguinal nodes up to 1-1.5cm may be normal in the absence of symptoms. In this case, they are very nonspecific nodes, without signs of malignancy (mobile, soft, not painful) that do not lead us to suspect neoplastic infiltration and the lack of other clinical signs also leads us to rule out the presence of STD.

The presence of inguinal nodes up to 1-1.5cm may be normal in the absence of symptoms. In this case, they are very nonspecific nodes, without signs of malignancy (mobile, soft, not painful) that [HIDDEN] and the lack of other clinical signs also leads us [HIDDEN].

A 24-year-old woman consults after noticing inguinal lymphadenopathy. The interrogation does not reveal any local discomfort or data suggestive of sexually transmitted infection. The examination revealed two lymphadenopathies, one in each groin, 1 cm in diameter, soft, mobile, non-painful. No skin lesions are seen on the lower limbs, anus or perineum. Which test do you consider essential?

A lues serology since it is most likely a Treponema pallidum infection.

A gynecological examination to rule out ovarian cancer.

By the clinical characteristics it seems to be normal lymph nodes and complementary explorations should not be done.

A Paul-Bunell test should be performed to rule out infectious mononucleosis.

Genital ulcer

Overview A genital ulcer may be located on the vulva, penis, perianal region, or anus. Globally, the incidence of genital ulcers is estimated to be approximately 20 million cases annually. The most likely cause of a genital ulcer varies depending on the characteristics of a population and location. The most common cause of genital ulcers in the United States is herpes simplex infections, with syphilis the second most common cause, and chancroid the third. These common causes of genital ulcer disease (HSV-1, HSV-2 and treponema pallidum) can all be efficiently transmitted through oral sex. Important signs associated with genital ulcers that may assist in the diagnosis of the cause of the genital ulcer may include the presence of tender or non-tender enlarged lymph nodes in the groin area, a painful or non-painful genital ulcer, or the presence of vesicular lesions, which are small, painful, elevated blisters.

Inguinal lymph nodes

Clinical significance The presence of swollen inguinal lymph nodes is an important clinical sign because lymphadenopathy (swelling) may indicate an infection, or spread as a metastasis from cancers, such as anal cancer and vulvar cancer. Inguinal lymph nodes may normally be up to 2 cm. The cut-off value for normal sized inguinal nodes is up to 10 mm. Additional images References Lymphatic organ anatomy

Inguinal lymphadenopathy

Inguinal lymphadenopathy causes swollen lymph nodes in the groin area. It can be a symptom of infective or neoplastic processes. Infective aetiologies include Tuberculosis, HIV, non-specific or reactive lymphadenopathy to recent lower limb infection or groin infections. Another notable infectious cause is Lymphogranuloma venereum, which is a sexually transmitted infection of the lymphatic system. Neoplastic aetiologies include lymphoma, leukaemia and metastatic disease from primary tumours in the lower limb, external genitalia or perianal region and melanoma. References Further reading Inflammations Diseases of veins, lymphatic vessels and lymph nodes

Lymphogranuloma venereum

The secondary stage most often occurs 10–30 days later, but can present up to six months later. The infection spreads to the lymph nodes through lymphatic drainage pathways. The most frequent presenting clinical manifestation of LGV among males whose primary exposure was genital is unilateral (in two-thirds of cases) lymphadenitis and lymphangitis, often with tender inguinal and/or femoral lymphadenopathy because of the drainage pathway for their likely infected areas. Lymphangitis of the dorsal penis may also occur and resembles a string or cord. If the route was anal sex, the infected person may experience lymphadenitis and lymphangitis noted above. They may instead develop proctitis, inflammation limited to the rectum (the distal 10–12 cm) that may be associated with anorectal pain, tenesmus, and rectal discharge, or proctocolitis, inflammation of the colonic mucosa extending to 12 cm above the anus and associated with symptoms of proctitis plus diarrhea or abdominal cramps.

InternalMed_Harrison

Diagnosis Although most genital ulcerations cannot be diagnosed confidently on clinical grounds alone, clinical findings (Table 163-7) FIGURE 163-5 Chancroid: multiple, painful, punched-out ulcers with undermined borders on the labia occurring after autoinoculation. Sexually Transmitted Infections: Overview and Clinical Approach FIGURE 163-6 Genital herpes. A relatively mild, superficial ulcer is typically seen in episodic outbreaks. (Courtesy of Michael Remington, University of Washington Virology Research Clinic.) FIGURE 163-7 Lymphogranuloma venereum (LGV): striking ten-der lymphadenopathy occurring at the femoral and inguinal lymph nodes, separated by a groove made by Poupart’s ligament. This “sign-of-the-groove” is not considered specific for LGV; for example, lym-phomas may present with this sign. InITIAL MAnAgEMEnT of gEnITAL oR PERIAnAL uLCER

[A chancre instead of cancer].

Syphilis (lues) is a sexually transmitted infection caused by the spirochete Treponema pallidum. In adolescents, the diagnosis of primary syphilis can be made promptly by taking a sexual medical history and inspecting the glans penis. A 17-year-old male was referred to the paediatric oncology centre for additional diagnostics due to inguinal lymphadenopathy, with a strong suspicion of a malignant lymphoma. None of the physicians took a sexual medical history or investigated the glans penis, as a result of which essential information was lacking. The combination of inguinal lymphadenopathy and the ultrasound findings for the inguinal region made the physicians only consider a malignancy. However, it actually concerned a reactive lymphadenopathy associated with primary syphilis. This case demonstrates that a full medical history and thorough physical examination can prevent the need for costly and invasive diagnostics.

Anatomy, Abdomen and Pelvis: Female External Genitalia -- Clinical Significance -- Sexually Transmitted Infections

Treponema pallidum : Syphilis infections result from Treponema pallidum . This infection usually manifests as a painless chancre in the primary stage. If the disease is left untreated, it will progress to the secondary stage. In the secondary stage, it manifests as fever, widespread maculopapular skin rashes involving the palms and soles,  widespread lymphadenopathy (epitrochlear node is pathognomic), and genital lesions similar to genital warts (condylomata lata- has a rounder surface when compared with condylomata acuminata). If there is still no treatment during the secondary stage, the infection will progress into the tertiary stage. The tertiary stage causes necrotic lesions called Gummas, neurological symptoms such as tabes dorsalis, Argyll Robertson pupils, and general paresis, cardiac symptoms such as aortitis. The treatment of syphilis is with the use of penicillin.

Gynecology_Novak

Several clinical presentations are highly suggestive of specific diagnoses: 1. A painless and minimally tender ulcer, not accompanied by inguinal lymphadenopathy, is likely to be syphilis, especially if the ulcer is indurated. A nontreponemal rapid plasma reagin (RPR) test, or venereal disease research laboratory (VDRL) test, and a confirmatory treponemal test—ﬂuorescent treponemal antibody absorption (FTA ABS) or microhemagglutinin–T. pallidum (MHA TP)—should be used to diagnose syphilis presumptively. Some laboratories screen samples with treponemal enzyme immunoassay (EIA) tests, the results of which should be confirmed with nontreponemal tests. The results of nontreponemal tests usually correlate with disease activity and should be reported quantitatively. 2.

Anatomy, Abdomen and Pelvis: Inguinal Lymph Node -- Introduction

The inguinal lymph node can be subdivided into the superficial and deep lymph nodes and collectively drains the anal canal(below the pectinate line), the skin below the umbilicus, lower extremity, scrotum, vulva, glans penis, and clitoris. The lymph node's primary function is to filter for harmful substances as lymphatic fluids travel through its cortex, paracortex, and medulla. Clinical signs of inguinal lymphadenopathy can help to clue physicians in possible diagnoses of sexually transmitted diseases such as syphilis, chancroid, and lymphogranuloma venereum. The lymph node can also serve to assist in the diagnosis of cancer.

Anatomy, Abdomen and Pelvis: Inguinal Lymph Node -- Clinical Significance -- Lymphadenopathy

Syphilis is a bacterial infection caused by the spirochete Treponema pallidum. Clinical presentation of secondary syphilis can present with diffuse lymphadenopathy along with fever, skin rashes, and condylomata lata. [7] Chancroid

Sexually Transmitted Infections -- History and Physical -- Granuloma Inguinale

Females and males: Signs and symptoms: Patients will present with highly vascularized lesions over the genitals and perineum that tend to be painless. [37] [38] It can cause severe scarring. Physical Exam: Typical findings include ulcer-like lesions that are beefy red, consistent with high vascularization that bleeds easily with manipulation. Subcutaneous granulomas may be present, but lymphadenopathy is uncommon. The lesions tend to be relatively large and irregular. It is often found to be associated with secondary infections. Four main lesions can be seen on examination: 1. Ulcerovegetative: large painless ulcer on the patient's physical exam. 2. Nodular: soft and erythematous that tend to ulcerate throughout the infectious process. 3. Cicatricial: dry ulcerations that tend to transition into plaques. 4. Hypertrophic: lesions are thick and painless. [37] [39]

Swollen lymph nodes usually indicate infection from bacteria or viruses. Swollen inguinal lymph nodes could indicate an infection of areas of the lower body. One of the more concerning causes of inguinal lymphadenopathy is sexually transmitted infections. Sexually transmitted infections that commonly presents with inguinal lymphadenopathy are lymphogranuloma venereum, secondary syphilis, and chancroid caused by Chlamydia trachomatis (L1-L3), Treponema pallidum , and Haemophilus ducreyi , respectively. Lymphogranuloma venereum

Yaws

Serological tests cannot distinguish yaws from the closely related syphilis; no test distinguishing yaws from syphilis is widely available. The two genomes differ by about 0.2%. PCR and DNA sequencing can distinguish the two. There are also no common blood tests which distinguish among the four treponematoses: syphilis (Treponema pallidum pallidum), yaws (Treponema pallidum pertenue), bejel (Treponema pallidum endemicum), and pinta (Treponema carateum). Haemophilus ducreyi infections can cause skin conditions that mimic primary yaws. People infected with Haemophilus ducreyi lesions may or may not also have latent yaws, and thus may or may not test positive on serological tests. This was discovered in the mid 2010s. It seems that a recently diverged strain of Haemophilus ducreyi has evolved from being a sexually transmitted infection to being a skin ulcer pathogen that looks like yaws. Yaws has been reported in nonendemic countries.

InternalMed_Harrison

node is an enlarged left supraclavicular node infiltrated with metastatic cancer from a gastrointestinal primary. Metastases to supraclavicular nodes also occur from lung, breast, testis, or ovarian cancers. Tuberculosis, sarcoidosis, and toxoplasmosis are nonneoplastic causes of supraclavicular adenopathy. Axillary adenopathy is usually due to injuries or localized infections of the ipsilateral upper extremity. Malignant causes include melanoma or lymphoma and, in women, breast cancer. Inguinal lymphadenopathy is usually secondary to infections or trauma of the lower extremities and may accompany sexually transmitted diseases such as lymphogranuloma venereum, primary syphilis, genital herpes, or chancroid. These nodes may also be involved by lymphomas and metastatic cancer from primary lesions of the rectum, genitalia, or lower extremities (melanoma).

Cervical lymphadenopathy

Cervical lymphadenopathy is a sign or a symptom, not a diagnosis. The causes are varied, and may be inflammatory, degenerative, or neoplastic. In adults, healthy lymph nodes can be palpable (able to be felt), in the axilla, neck and groin. In children up to the age of 12 cervical nodes up to 1 cm in size may be palpable and this may not signify any disease. If nodes heal by resolution or scarring after being inflamed, they may remain palpable thereafter. In children, most palpable cervical lymphadenopathy is reactive or infective. In individuals over the age of 50, metastatic enlargement from cancers (most commonly squamous cell carcinomas) of the aerodigestive tract should be considered. Classification Cervical lymphadenopathy can be thought of as local where only the cervical lymph nodes are affected, or general where all the lymph nodes of the body are affected. Causes

InternalMed_Harrison

adenopathy that is sometimes mistaken for malignancy; syphilis, LGV, HSV infection, and chancroid involving the anus can produce inguinal adenopathy because anal lymphatics drain to inguinal lymph nodes.

Unusual Manifestations of Secondary Syphilis: Case Presentations.

Dear Editor, Syphilis is an infection caused by Treponema pallidum. Without treatment, it goes through the following stages: primary, secondary, latent, and tertiary (1). The clinical picture of secondary syphilis is very variable (2,3). We present two rare cases of secondary syphilis, one with nodular lesions initially considered to be lymphoma and second with periostitis, which was initially interpreted as an osteoma. To date, only 15 cases with nodular lesions and 10 cases with periostitis in secondary syphilis have been reported in the literature. The first patient was a 59 year old man who presented in a private practice with nodular lesions on the face and axillary and inguinal folds (Figure 1, a, b). The initial diagnostic consideration was lymphoma. A biopsy specimen was taken, and the histopathological features revealed epidermal hyperplasia with papillomatosis, minimal spongiosis with many neutrophils and with a marked inflammatory infiltrate in dermis, consisting of lymphocytes, plasma cells, and neutrophils; the diagnosis of interfaced dermatitis was established (Figure 1, d, e). After one month, the patient presented to our clinic with numerous nodular lesions, some of them painful, located on the trunk and intertriginous folds, including the intergluteal cleft - the lesions in this area being suggestive of condylomata lata (Figure 1, c). The diagnosis of secondary syphilis was taken into consideration, and screening serum tests were performed and found reactive: a Venereal Diseases Research Laboratory (VDRL) titer of 1:64 and Treponema pallidum Hemaglutination Assay (TPHA) titer of 1:80. Hepatitis and anti-human immunodeficiency virus (HIV) antibodies serology was negative. The biopsy was repeated and showed the same histopathological changes. In addition, Warthin-Starry staining was performed, revealing the presence of some spiral micro-organisms in the dermis corresponding to Treponema pallidum (Figure 1, f). A diagnosis of secondary syphilis was established, and the patient was treated with benzathine penicillin G 2.4 million units by intramuscular injection once a week for 2 consecutive weeks. The skin lesions regressed within 1 month, and serological tests showed a VDRL titer of 1:8 3 months after treatment. The second patient was a homosexual male, 35 years old, diagnosed with HIV infection, stage B2. He presented with bone pain in the calves and forearms, with insidious onset. He also presented with an associated erythematous maculo-papular rash on the trunk and limbs and generalized lymphadenopathy (Figure 2, a, b). The tibial crest and radius were sensitive to palpation. A right leg radiography was performed, raising suspicion of osteoid osteoma. The CT scan excluded the diagnosis of osteoma; taking into account the epidemiological context, the diagnosis of syphilis was suspected. The diagnosis was confirmed by leg ultrasound examination (2D US) which showed thickening of the compact tibial bone associated with subperiosteal destructive and proliferative changes (Figure 2, c, d) and by serology for syphilis: the VDRL titer was 1:32 and the TPHA titer was 1:80. The patient was treated with benzathine penicillin 2.4 million units, once a week, for 2 consecutive weeks, with clinical improvement. Syphilis continues to be a serious public health problem worldwide, even if it is a controllable disease due to diagnostic tests and effective and accessible treatment. According to the World Health Organization in 2008, the estimated number of new cases of sexually transmitted diseases in adults with syphilis is 10.6 million cases (4). The cases presented in this paper were characterized by unusual manifestations, requiring good collaboration between the dermatologist and other specialties. In the first case, the diagnosis of secondary syphilis was confirmed by positive serological, clinical, and histopathological findings. The main differential diagnosis of nodular syphilis includes lymphoma, sarcoidosis, Kaposi's sarcoma, atypical mycobacteriosis, deep fungal infections, leprosy, tuberculosis, leishmaniasis, and lymphomatoid papulosis (5). Another important differential diagnosis is between secondary and tertiary syphilis, especially when ulcerating nodules are present. Tertiary syphilis is characterized by unilateral, deep ulcerating nodules with necrotizing granulomas (6). Bone involvement during syphilis is mainly represented by polyarthritis, synovitis, osteitis, and periostitis (7,8). Syphilitic periostitis is characterized by localized or diffuse pain, particularly during the night, which is relieved by movement. The skull, the shoulder girdle, and the long bones are the most common sites of involvement (9). In conclusion, we presented two different cases of secondary syphilis that contribute to the clinical experience of rare cases presented in the literature, raising the awareness of dermatologists and other specialists about less specific clinical aspects of syphilis.

Sexually Transmitted Infections -- History and Physical -- Lymphogranuloma venereum (LGV)

Females and males: Signs and symptoms: Patients will present with painful lymphadenopathy localized to the inguinal area. Patients may note the initial presentation of a pustule that gradually progresses to large painful ulceration. [41] Men tend to present with early or acute stages, while women typically present much later. [19] Physical Exam: Lymphogranuloma venereum presents with two stages: Primary phase is a small painless papule/pustule that will ulcerate and can be visualized throughout the affected genital area. During the secondary phase, patients present with unilateral lymphadenopathy that is fluctuant with palpation or may be suppurative in a presentation known as buboes. [38] Buboes tend to rupture in the acute phase and progress to a thickened mass. [42]

InternalMed_Harrison

Lymphadenopathy may be an incidental finding in patients being examined for various reasons, or it may be a presenting sign or symptom of the patient’s illness. The physician must eventually decide whether the lymphadenopathy is a normal finding or one that requires further study, up to and including biopsy. Soft, flat, submandibular nodes (<1 cm) are often palpable in healthy children and young adults; healthy adults may have palpable inguinal nodes of up to 2 cm, which are considered normal. Further evaluation of these normal nodes is not warranted. In contrast, if the physician believes the node(s) to be abnormal, then pursuit of a more precise diagnosis is needed. APPROACH TO THE PATIENT:

Sexually Transmitted Infections -- History and Physical -- Chancroid

Females and males: Signs and symptoms: Often occurs in the 20 to 30-year-old age group, frequently among sex workers and their clients. The areas most often affected include the distal portion of the penis in men, while in women, the vagina, labia, and perianal regions are involved. The most significant symptom is the extremely high pain level noted when the lesion reaches the ulcerative stage. [6] Physical Exam: The lesion starts as a reddish papule which rapidly progresses to a pustule followed by an extremely painful ulcer. The ulcer sometimes called a "soft chancre," will have soft and irregular margins with a friable base and a grayish-yellowish exudate. It tends to bleed easily. The ulcers are typically 1 cm to 2 cm in diameter and usually resolve spontaneously within three months, even if left untreated. Close to half of the affected individuals will develop regional lymphadenopathy, which may be tender. A minority (about 25%) of these patients will progress to infected bulla or abscesses, which can rupture and become superinfected leading to significant tissue destruction and damage to the genitalia. It is estimated that 10% of affected individuals will also have syphilis or genital herpes as well.

InternalMed_Harrison

Approach to the Patient with an Infectious Disease regions (e.g., popliteal, inguinal, epitrochlear, axillary, multiple cervical regions), with notation of the location, size (normal, <1 cm), presence or absence of tenderness, and consistency (soft, firm, or shotty) and of whether the nodes are matted (i.e., connected and moving together). Of note, palpable epitrochlear nodes are always pathologic. Of patients presenting with lymphadenopathy, 75% have localized findings, and the remaining 25% have generalized lymphadenopathy (i.e., that involving more than one anatomic region). Localized lymphadenopathy in the head and neck region is found in 55% of patients, inguinal lymphadenopathy in 14%, and axillary lymphadenopathy in 5%. Determining whether the patient has generalized versus localized lymphadenopathy can help narrow the differential diagnosis, as various infections present differently.

Lymphadenopathy

Lymph node enlargement is recognized as a common sign of infectious, autoimmune, or malignant disease. Examples may include: Reactive: acute infection (e.g., bacterial, or viral), or chronic infections (tuberculous lymphadenitis, cat-scratch disease). The most distinctive sign of bubonic plague is extreme swelling of one or more lymph nodes that bulge out of the skin as "buboes." The buboes often become necrotic and may even rupture. Infectious mononucleosis is an acute viral infection usually caused by Epstein-Barr virus and may be characterized by a marked enlargement of the cervical lymph nodes. It is also a sign of cutaneous anthrax and Human African trypanosomiasis Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy (Piringer-Kuchinka lymphadenopathy). Plasma cell variant of Castleman's disease - associated with HHV-8 infection and HIV infection

Scrotal lymphangioma circumscriptum.

Lymphangioma circumscriptum (LC) is anuncommon, benign, cutaneous disorder thatinvolves lymphatic dilatation to cause vesicularand papular lesions on the trunk, extremities, andanogenital areas. It may be a diagnostic challengewhen appearing in the anogenital region andoften is misdiagnosed and mistreated as infectiousetiologies, which include molluscum contagiosumand condylomata accuminata. We report a healthy40-year-old man with a six-month history of aneruption of multiple, asymptomatic, scrotal papulesthat were diagnosed as lymphangiomas. Awarenessof scrotal LC in adult men without prior disease orsymptoms is necessary for proper diagnosis andavoidance of unnecessary treatment.

Sézary disease

Generalized erythroderma– redness of the skin Lymphadenopathy – swollen, enlarged lymph nodes Atypical T-cells – malignant lymphocytes known as "Sézary cells" seen in the peripheral blood with typical cerebriform nuclei (brain-shaped, convoluted nuclei) Hepatosplenomegaly– enlarged liver and spleen Palmoplantar keratoderma – thickening of the palms of the hands, and soles of the feet Diagnosis Those who have Sézary disease often present with skin lesions that do not heal with normal medication. A blood test generally reveals any change in the levels of lymphocytes in the blood, which is often associated with a cutaneous T-cell lymphoma. Finally, a biopsy of a skin lesion can be performed to rule out any other causes.

InternalMed_Harrison

The presentation of chancroid does not usually include all of the typical clinical features and is sometimes atypical. Multiple ulcers can coalesce to form giant ulcers. Ulcers can appear and then resolve, with inguinal adenitis (Fig. 182-2) and suppuration following 1–3 weeks later; this clinical picture can be confused with that of lymphogranuloma venereum (Chap. 213). Multiple small ulcers can resemble folliculitis. Other differential diagnostic considerations include the various infections causing genital ulceration, such as primary syphilis, secondary syphilis (condyloma latum), genital herpes, and donovanosis. In rare cases, chancroid lesions become secondarily infected with bacteria; the result is extensive inflammation. FIGURE 182-2 Chancroid with characteristic penile ulcers and associated left inguinal adenitis (bubo).

Primary syphilis of the oropharynx: an unusual location of a chancre.

A 33-year-old man presented with a two-week history of an asymptomatic ulcer of the oropharynx and submandibular lymph nodes swelling. Laboratory examinations were normal, but serological tests revealed positivity for rapid plasma reagin, Treponema pallidum haemagglutination assay and anti-T. pallidum IgM antibodies. Since the patient denied any homosexual relationship, a biopsy of the lesion was performed, which confirmed primary syphilis. The patient received an intramuscular injection of Benzathine Penicillin G (2.4 MU) with complete resolution of the lesion. Extragenital chancres occur in at least 5% of patients with primary syphilis, and the oral mucosa is the most frequent location as a consequence of orogenital/oroanal contact with an infectious lesion. Because of their transient nature, these oral ulcerations are often underestimated by the patient or by any unsuspecting clinician. Health professionals should consider the recent sexual history of their patients and should be prepared to recognise oral and systemic manifestations of sexually transmitted infections.

Chancroid

About half of infected men have only a single ulcer. Women frequently have four or more ulcers, with fewer symptoms. The ulcers are typically confined to the genital region most of the time. The initial ulcer may be mistaken as a "hard" chancre, the typical sore of primary syphilis, as opposed to the "soft chancre" of chancroid. Approximately one-third of the infected individuals will develop enlargements of the inguinal lymph nodes, the nodes located in the fold between the leg and the lower abdomen. Half of those who develop swelling of the inguinal lymph nodes will progress to a point where the nodes rupture through the skin, producing draining abscesses. The swollen lymph nodes and abscesses are often referred to as buboes.

Oropharyngeal lesions and cervical lymphadenopathy: syphilis is a differential diagnosis that is still relevant.

Syphilis (lues), a chronic infectious disease caused by Treponema pallidum, has been increasing in incidence during the last few years. Therefore, while clinically it is often not suspected, syphilis is increasingly becoming a differential diagnosis in routine pathology. To report our experience with five cases of cervical lymphadenopathy and/or oropharyngeal lesions, clinically thought to be lymphomas, lymph node metastases or carcinoma, in which we made the mostly clinically unsuspected diagnosis of syphilis. Fine needle aspiration of enlarged cervical lymph nodes was evaluated by cytology and flow cytometry (fluorescence-activated cell sorting analysis), and biopsies were examined by using histology. In addition, all materials were also subjected to immunostaining, silver staining and molecular (PCR) testing. Fine needle aspiration cytology revealed follicular hyperplasia in two cases and granulomatous lymphadenitis in one case. In three patients, concomitant biopsy of co-existing oropharyngeal lesions revealed histological findings compatible with syphilis. T pallidum was detected in all cytological and histological samples by immunohistochemistry/immunocytochemistry and PCR. Subsequently, a diagnosis of syphilis was confirmed clinically and by serology. Syphilitic lymphadenitis is still a relevant differential diagnosis of cervical lymphadenopathy, and it is clinically often not suspected. Co-existing oropharyngeal lesions should alert the physician to this differential diagnosis; and lesions with compatible morphology should be tested with immunohistochemistry and immunocytochemistry and/or molecular analysis to confirm the diagnosis of syphilis.

Sexual health clinic

In a private room or space, the patient will partially undress. The clinician may inspect the patient's: Throat and lymph nodes of the neck for inflammation Pubic hair for lice Lymph nodes of the groin for swelling Genitals, anus, and surrounding areas for sores and warts The clinician may swab the patient's: Throat to test for gonorrhea and possibly chlamydia Cheek, inside, to diagnose HIV Sores of the genitals, anus, and surrounding areas to test for herpes Urethra to test for gonorrhea and possibly chlamydia Vagina to test for chlamydia and possibly gonorrhea Cervix to test for cervical intraepithelial neoplasia (a Pap test) Rectum to test for gonorrhea and possibly chlamydia The clinician may take small blood samples by pricking a finger or from a vein to test for HIV, syphilis, and possibly herpes and hepatitis C.

Disseminated lupus vulgaris.

A 28-year-old woman presented with reddish raised, shiny lesions over the face and ears present for the past 3 years. Four years ago, she developed in her left axilla a nodule that became fluctuant and tender, which ruptured to discharge seropurulent material. It subsided after the patient had received antibiotics for 6 months, leaving puckered scarring. There was no history of antituberculous treatment. After 1 year, she developed papulonodular lesions on her face, nose, and ears. There was now a history of malaise, fever, dry cough, and anorexia and weight loss for the past 2 months. The patient was fully vaccinated in childhood, including against varicella infection. The general physical examination revealed lymphadenopathy involving cervical, axillary, and inguinal lymph nodes 0.5 x 0.5 cm to 1 x 1.5 cm, firm in consistency, and nontender. They were discrete except in the left axilla where multiple matted lymph nodes were present with overlying scarring and a papule. Her systemic examination was normal. Cutaneous examination showed a shiny erythematous plaque 3x2 cm with central atrophy and scarring on the face (Figure). It was comprised of multiple shiny nontender soft papules arranged in annular configuration. Similar discrete papules and nodules with adherent fine scaling were seen bilaterally on the alar prominence of the nose, lower lip, and post-auricular area. On diascopy, apple jelly nodules were seen. The hemogram, liver function tests, and renal function tests were normal, except for an elevated erythrocyte sedimentation rate. The Mantoux test showed erythema and an induration of 20 x 20 cm. A posteroanterior view on the chest x-ray showed fibrotic changes suggestive of pulmonary tuberculosis. Ultrasonography of the abdomen and pelvis showed no tubercular foci. Human immunodeficiency virus serology by enzyme-linked immunosorbent assay with 3 different kits was nonreactive. Histopathology from a nodule showed a focally thinned-out epidermis with follicular plugging and multiple epithelioid cell granulomas, rimmed by lymphocytes in the deeper portion of the dermis, mainly peri-appendageal. Stain for acid-fast bacteria was negative. Cultures from the skin lesions were negative. The patient was diagnosed as having lupus vulgaris with multiple lesions of varying morphology at different sites with pulmonary tuberculosis and healed lymph node involvement.

[Peripheral lymphadenopathy in childhood--recommendations for diagnostic evaluation].

Enlargement of peripheral lymph nodes most commonly caused by a local inflammatory process is frequently seen in childhood. The aim of the present study was to analyze the most common causes of peripheral lymphadenopathy and to develop a simple algorithm for the primary diagnostic evaluation of peripheral lymph node enlargement in this age group. Between April and September 1999 87 unselected children (median age: 5 1/2 years) with peripheral lymphadenopathy were referred to the Department of Pediatrics, University of Graz, for further investigation. EBV infection was diagnosed in 20 (23.0%) children. 19 (21.8%) patients had acute bacterial lymphadenitis. In 21 (24.1%) patients lymph node enlargement was classified as "post/parainfectious (viral)". Four patients each had toxoplasmosis and cat scratch disease. In 11 (12.6%) patients neither physical nor laboratory examinations revealed pathologic results. Among the remaining 8 children sarcoidosis and Hodgkin disease was diagnosed in one patient each. Small, soft, mobile, nontender, cervical, axillary or inguinal lymph nodes do not require further investigations. In case of enlarged, tender lymph nodes with overlying skin erythema and fever diagnostic evaluation should include complete blood count, erythrocyte sedimentation rate and/or c-reactive protein level, supplemented by appropriate antibody testing (EBV, CMV, Toxoplasma gondii, Bartonella henselae). Firm, enlarged, painless lymph nodes which are matted together and fixed to the skin or underlying tissues necessitate a more detailed diagnostic evaluation in order to exclude malignant or granulomatous diseases. Our study demonstrated that primary diagnostic evaluation of childhood peripheral lymphadenopathy is mainly based on clinical grounds. In most cases a small number of additionally performed laboratory tests allow to correctly identify the cause of the peripheral lymph node enlargement.

Gynecology_Novak

3. One to three extremely painful ulcers, accompanied by tender inguinal lymphadenopathy, are unlikely to be anything except chancroid. This is especially true if the adenopathy is ﬂuctuant. 4. An inguinal bubo accompanied by one or several ulcers is most likely chancroid. If no ulcer is present, the most likely diagnosis is LGV. Recommended regimens for the treatment of chancroid include azithromycin, 1 g orally in a single dose; ceftriaxone, 250 mg intramuscularly in a single dose; ciproﬂoxacin, 500 mg orally twice a day for 3 days; or erythromycin base, 500 mg orally four times daily for 7 days. Patients should be reexamined 3 to 7 days after initiation of therapy to ensure the gradual resolution of the genital ulcer, which can be expected to heal within 2 weeks unless it is unusually large.


This question corresponds to the section on traumatology; however, it could be answered with knowledge of rheumatology and with the osteoporosis recommendations of the Spanish Society of Rheumatology. In osteoporosis, one of the main risks associated with increased fracture risk is low adherence to treatment, so answer 1 is correct. Answer 2 is found in the SER guidelines, which confirm that some studies conclude that bone remodeling markers can be useful for early monitoring of adherence and response to treatment. Answer 4 is correct because again in the SER 2019 guidelines they quote: "The current scientific evidence allows us to affirm that neither increasing dietary calcium nor taking calcium supplements alone protects against the appearance of fractures". Therefore, the correct answer to this question is option 3. Patients on pharmacological treatment for OP should use calcium and vitamin D supplements because practically all clinical trials that have demonstrated efficacy of antiosteoporotic drugs routinely include calcium supplements and cholecalciferol (vitamin D3), but not in monotherapy.

This question corresponds to the section on traumatology; however, it could be answered with knowledge of rheumatology and with the osteoporosis recommendations of the Spanish Society of Rheumatology. In osteoporosis, one of the main risks associated with increased fracture risk is low adherence to treatment, so [HIDDEN]. Answer 2 is found in the SER guidelines, which confirm that some studies conclude that bone remodeling markers can be useful for early monitoring of adherence and response to treatment. [HIDDEN] because again in the SER 2019 guidelines they quote: "The current scientific evidence allows us to affirm that neither increasing dietary calcium nor taking calcium supplements alone protects against the appearance of fractures". Therefore, [HIDDEN]. Patients on pharmacological treatment for OP should use calcium and vitamin D supplements because practically all clinical trials that have demonstrated efficacy of antiosteoporotic drugs routinely include calcium supplements and cholecalciferol (vitamin D3), but not in monotherapy.

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 such fractures in non-institutionalized elderly.

Increasing dietary calcium or taking calcium supplements alone 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women.

Increased dietary calcium intake has been proposed as a population-based public health intervention to prevent osteoporotic fractures. We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action. Five-year, double-blind, placebo-controlled study of 1460 women recruited from the population and older than 70 years (mean age, 75 years) who were randomized to receive calcium carbonate, 600 mg twice per day, or identical placebo. The primary end points included clinical incident osteoporotic fractures, vertebral deformity, and adverse events ascertained in 5 years. Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body, quantitative ultrasonography of the heel, and peripheral quantitative computed tomography of the distal radius. Among our patients, 16.1% sustained 1 or more clinical osteoporotic fractures. In the intention-to-treat analysis, calcium supplementation did not significantly reduce fracture risk (hazard ratio, 0.87; 95% confidence interval, 0.67-1.12). However, 830 patients (56.8%) who took 80% or more of their tablets (calcium or placebo) per year had reduced fracture incidence in the calcium compared with the placebo groups (10.2% vs 15.4%; hazard ratio, 0.66; 95% confidence interval, 0.45-0.97). Calcium-treated patients had improved quantitative ultrasonography findings of the heel, femoral neck and whole-body dual x-ray absorptiometry data, and bone strength compared with placebo-treated patients. Of the 92 000 adverse events recorded, constipation was the only event increased by the treatment (calcium group, 13.4%; placebo group, 9.1%). Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance, but it is effective in those patients who are compliant.

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.

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.

Eldecalcitol

Treatment for Osteoporosis Eldecalcitol can be used for the treatment of hypocalcaemia or osteoporosis. Calcium absorption increases with the presence of eldecalcitol by the body, occurring in the intestines, which is useful for those who have low calcium levels. Eldecalcitol is more often used due to its effects to treat osteoporosis. In the aging population, the bone matrix becomes weakened through untreated osteoporosis. This leads to an increased risk of severe fractures that include spinal and hip fractures in addition to vertebral and wrist fractures. This creates a burden on the health care system due to a decline in the quality of life for the individuals that suffer from this condition. Some risk factors leading to the predisposition of developing osteoporosis are previous incidents of bone fractures and a reduction in bone mineral density. These factors expectantly increase as age increases.

Women's Health Initiative

Calcium/vitamin D The calcium/vitamin D (CaD) trial component was designed to test the hypothesis that women taking a combination of calcium and vitamin D will experience a reduced risk of hip and other fractures, as well as breast and colorectal cancer. Women participating in this intervention were randomly assigned to receive a regimen of 1000 mg calcium in combination with 400 International Units (IU) of vitamin D (n = 18176) or a placebo (n = 18106), and were followed for an average of 7 years, with monitoring for bone density, fractures, and pathologically confirmed cancers as the measures of outcomes. Women in the CaD trial were already participating in the HT trial, the DM trial, or both. In addition to the global exclusion criteria, component-specific exclusion criteria hypercalcemia, renal calculi, corticosteroid use, and calcitriol use.

[Update on treatment of postmenopausal osteoporosis].

The most frequent sites of osteoporotic fractures are the vertebrae, the hip, the forearm and the proximal humerus. Drugs that inhibit bone resorption constitute the mainstay for the treatment of postmenopausal osteoporosis. A recent meta-analysis indicates that vitamin D can reduce the risk of hip fractures only if calcium supplements are also administered. The effect of hormone replacement therapy on the risk of non vertebral fractures is less clear than on vertebral fractures. Raloxifene (a SERM) reduces the rate of vertebral fractures and of breast cancer, but it does not protect against hip fracture. Bisphosphonates are the most commonly used compounds to treat postmenopausal osteoporosis. The level of evidence for currently used bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) to reduce vertebral fracture rate is maximal. Results of controlled clinical trials indicate a reduction in the risk of vertebral fractures of 40-50% and of 20-40% for non vertebral fractures, including hip fractures. However, their relative efficacy on hip fractures has been less well studied and remains more controversial. Long-term compliance of bisphosphonate therapy is improved by intermittent schemes. The most recent developpements concern the intravenous administration of ibandronate and even more of zoledronate (yearly infusions). The reduction in the rate of vertebral and hip fractures has been demonstrated in the main zoledronate trial and a prolongation of survival has been shown in the study including patients with a recent hip fracture. Whereas hyperparathyroidism is a cause of bone loss, the intermittent administration of parathyroid hormone or of its 1-34 fragment (teriparatide) exerts anabolic effects on the skeleton. The treatment is demanding and costly (daily sc injections during 18 months), requires some monitoring (serum and urinary calcium) but the results, at least for vertebral fractures, are quite favorable. Strontium ranelate is a less powerful stimulator of bone formation but it also reduces bone resorption. Its daily administration for 3 years reduces the risk of vertebral fractures and, to a lesser extent, of non vertebral fractures. Lastly, denosumab is a high affinity antibody against RANK Ligand that specifically blocks the formation and the activity of osteoclasts. The efficacy of this promising compound will soon be known.

Canadian health claims for food

In total, 63 897 individuals were analysed, most of whom were women (n=58 785 [92%]) with a mean age of 67.8 years (SD 9.7). 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. 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).