the advancing age is associated with profound changes in body composition , including increased fat mass , decreased fat - free mass ( particularly muscle ) , decreased total body water and decreased bone density ( 1 ) .
bone itself presents an organ of particular interest in both medical and pharmacological sciences . in medical sciences because of its unique physiology , since it undergoes remodeling throughout the lifespan with faster formation in the youth and faster resorption by growing older ( 2 ) .
bone is important in pharmacological sciences since different medications can either improve or worsen bone health , with different studies having analyzed the link between drug use and adverse effects in msh , some of which even resulted in potentially serious consequences such as drug - induced osteoporosis ( 3 , 4 , 5 ) .
corticosteroids seem to be the leading cause of secondary osteoporosis ( 5 , 6 ) , with many other medication groups seeming to increase the risk , such as thyroxine overdose , gonadotropin - releasing hormone ( gnrh ) agonists , aromatase inhibitors , thiazolidines , ppi ( proton pump inhibitors ) , loop diuretics , anticoagulant drugs , tricyclic antidepressants , anticonvulsant ( 7 ) which are still under scientific debates and investigations .
while the regular controlled prescription presents a common standard in every developed country , in a developing , low income country such as kosova ( 8) , it is generally believed that there are major problems regarding self - medication and usage of different medicines without the professional prescription .
these might result in higher risk of unsafe usage of medicines , declining the efficacy and increasing the overall price of treatment .
unfortunately , there are very few published studies carried out in kosovo concerning drug use , side effects , drug - drug interactions ( 4 , 9 , 10 , 11 ) .
this directly contributed to the main aims of this study , that are : 
 having an overview regarding the msh status of mature adults ( 40 - 65 years old ) in kosovo , finding out the impact of specific medications on adults msh . 
 
having an overview regarding the msh status of mature adults ( 40 - 65 years old ) in kosovo , finding out the impact of specific medications on adults msh .
we hypothesized that our subjects should be physically active enough to fulfill the international recommendations , while some medication groups discussed for their possible ( contradicting ) effect on msh such as n05b , a02b ( ppi , h2ra ) , h02ab , might have an impact on their msh , which could directly be affecting them .
especially since these medications are proved to be highly consumed within the studied group ages ( 40 - 65 ) ( 12 , 13 , 14 ) , there is an increasing prevalence of poly - pharmacy by age ( 12 ) , and the increasing risk of drug - drug interactions and adverse effects with the number of drugs used ( 12 , 13 ) .
this is an observational , cross - sectional study , designed and implemented in accordance with the current version of the declaration of helsinki of ethical principles regarding human experimentation ( 14 ) .
this study was approved by the committee of ethical and professional issues of university clinical center of kosova ( 797 - 12/03/2015 ) , while every participant was informed about procedures of this research and consciously signed a consent for participation and publication before the measurements .
a total number of 162 subjects ( 53 or 32.7% males and 109 or 67.3% females ) aged between 40 to 65 years old , residents of kosova , were recruited .
participants were randomly selected after announcements in the local media ( radio and tv stations ) and social networks ( facebook and twitter ) , and after fulfilling the inclusion criteria .
each subject s weight and height was measured with clinical scale and stadiometer ( respectively ) , with a precision of 100 g ( weight ) and 1 mm ( height ) .
inclusion criteria were males and females aged 40 - 65 , who have not been previously diagnosed with osteoporosis or osteopenia and ( consequently ) not being treated for that , patients with any conditions where x - ray radiation is counter - indicated and those with long term immobilizations . for analyzing medications effect on msh , patient that have been using the chosen medications for at least 6 months within the last 2 years were recruited . a random general healthcare status questionnaire provided by university clinical center of kosova ( ucck ) , was used for inclusion criteria .
bmq1 ( brief medication questionnaire 1 ) combined with additional questions for adherence of medicines use ( 15 , 16 ) were used to evaluate medicine usage , timeline frame of their usage and the origin of prescription / suggestion , in order to analyze reference and reliability of the subjects to information regarding medicines use .
medications in this study are grouped according to atc code ( anatomical therapeutic chemical classification system ) . international physical activity questionnaire ( 17 ) , translated and updated in albanian from boshnjaku a et al ( 18 ) , was used to assess the participants physical activity level , calculated as metabolic equivalent for task ( met)/hour .
self - administered nutritional standard questionnaire ( nsq ) ( 19 ) , modified by members of the department of health sciences , university of rome  foro italico  , was used to assess nutritional intakes in our study subjects .
bone density was measured on the distal radial bone of non - dominant arm by dxa scan ( dual energy x - ray absorptiometry ) , with a host software version 3.9.4 .
isometric hand grip strength was measured with electronic dynamometer ( saehan corporation , masan , korea ) , while in a sitting position when subjects squeezed for maximal isometric contraction in a duration of 45 seconds .
all statistical analyzes were applied using the program graph pad prism 6 for statistical analysis and statistical significance set at p < 0.05 .
differences between groups with continual data were performed using unpaired t test with welch s correction ( to compare two groups ) , one - way anova ( to compare three groups ) and multi - way anova ( to compare more than three groups ) , whereas the differences between categorical variables were made by using x test .
descriptive statistics for bio - anthropometric and physical activity ( pa ) level results are shown in table 1 .
male and female subjects enrolled in this study did not differ significantly in terms of age and weight ( p>0.05 ) , which was not the case in height and bmi ( p<0.05 ) .
participants characteristics surprisingly , there were no significant differences in terms of nutritional habits between genders , except for milk product consumption ( males consuming on average 2.190.48 rations per day , comparing to females 1.910.7 ) ( data not shown ) . despite 41.5% of males and 22% of females reporting to be low alcohol consumers , since no differences in any
parameter analyzed were detected , we decided to consider them as homogeneous groups . when analyzing variables amongst our study participants ( table 2 ) , significant differences ( p<0.05 ) were found in bmd and t - score but not on z - score ( p>0.05 ) between genders .
similar results were observed in hand grip ( table 3 ) , where males generated significantly higher force ( p<0.05 ) .
42% of total participants met the diagnostic criteria ( 20 ) of osteopenia ( 18.8% of males and 51.3% of females ) , out of which ( total subjects ) 6.8% are on the verge of getting osteoporosis ( with t - score below -2 ) with menopausal woman being at the greatest risk ( 11.6% ) .
no one met the diagnostic criteria of osteoporosis . when comparing the possible differences in study subjects that consumed n05b ( anxiolytics ) drugs comparing to those that do nt ( table 3 ) ,
no significant differences ( p>0.05 ) in any variables were found in total , males and females except for hand grip in females ( p<0.05 ) . in contrary to that , when analyzing h02ab medication group ( glucocorticoids ) between consumers and non - consumers , significantly better results ( p<0.05 ) were registered in all variables except hand grip strength ( p>0.05 ) in total subjects , in females and male consumers ( table 3 ) .
it was interesting to see that amongst the subjects consuming a02b drugs ( drugs for peptic ulcer and gastro - oesophageal reflux disease 
gord ) no significant differences in bmd , t - score and z - score were found ( p>0.05 ) comparing to those that do nt , whereas significantly better results ( p<0.05 ) were registered in hand grip isometric strength only ( table 4 ) .
the same situation was encountered within males ( consumers versus non - consumers ) in bmd , t - score , z - score and hand grip , whereas significantly better results were recorded in all variables in females . when dividing the a02b drug consumers into two subgroups : ppi and h2 receptor antagonists , significantly higher ( p<0.05 ) impact on bmd , t - score , z - score and hand grip isometric strength had ppi usage comparing to h2ra , but nevertheless this was nt the case when comparing each of these groups with the rest of this study subjects ( non - consumers of a02b ) ( table 4 ) .
t - n05b+ total consumers t - h02ab+ total consumers , t - n05b- total non - consumers t - h02ab- total non - consumers , m - n05b+ male consumers m - h02ab+ male consumers , m - n05b- male non - consumers m - h02ab- male non - consumers , f - n05b+ female consumers f - h02ab+ female consumers , f - n05b- female non - consumers f - h02ab- female non - consumers , a02b medication group consumers , t - a02b+ total consumers- t - ppi+ total consumers , t - a02b- total non - consumers - t - h2ra+ total consumers , m - a02b+ male consumers - t - a02b+ total consumers , m - a02b+ male non - consumers , f - a02b+ female consumers .
our study shows that the prevalence of osteoporosis ( po ) and osteopenia ( popen ) in kosovo seems to be lower than in several developed countries , such as sweden 
po 6% in women and 2.5% men ( aged > 50 ) ( 21 ) , uk 
po 24% and popen 49% in women ( 7 decade , either hip , spine or both ) ( 22 ) , korea 
po 30.6% ( 45 - 64years old in lumbar spine ) ( 23 ) , as well as in other developing countries , including here the latin american countries - po vertebral 12 - 18% and 8 - 22% proximal femur ( aged > 50 ) ( 24 ) , as well as china 
the gender distribution of osteopenia was in line with the current world prevalence being much higher in females ( 51.3% ) comparing to males ( 18.8% ) .
in fact , a previous study of ours ( 18 ) raised concerns regarding the msh of young females ( aged 17 - 30 years old ) in kosova comparing to their counterparts in developing countries , but this was not the case in this study .
perhaps the higher levels of pa amongst our study participants ( 2.260.76 in total , 2.40.68 in females and 1.980.83 in males ) comparing to young adult females from the other study ( 1.10.3 ) ( 18 ) might be playing a role in the general results . within the contradicting studies regarding the effect of n05b drugs ( including benzodiazepines : alprazolam , diazepam , bromazepam , lorazepam , midazolam ) in msh of consumers comparing to non - consumers ,
the comparison within our study was in line with other similar studies results regarding the lack of association between benzodiazepines usage and reduce in bone mineral density ( 26 , 27 ) , as well as the association between benzodiazepines usage and the improve in hand grip strength ( 28 ) .
when comparing our study findings with other already published studies regarding the possible impact of the usage of h02ab drugs ( methylprednisolone , dexamethasone ) in their consumers msh comparing to non - consumers , similar significant results ( p<0,05 ) were found with the majority of the up to date published data , allowing us to stay in line with the known facts of the existing correlation between glucocorticoids usage and osteoporosis ( 5 , 6 , 29 ) .
interesting results were observed when analyzing the possible effects of a02b medication group ( ppi inhibitors : pantoprazole , omeprazole , lansoprazole , esomeprazole and h2 antagonists : ranitidine ) in subjects that have been consuming them , where no significant differences ( p>0.05 ) were found in all bone variables and significant differences ( p<0.05 ) were found only in hand grip isometric strength in total subjects and in males . yet
, significant differences ( p<0.05 ) between female consumers and no consumers were found in all variables , supporting findings from van der hoorn study ( 30 ) , and suggesting that the prescription of a02b medication group should be especially careful when prescribing in middle aged or elderly females .
we believe that significant differences ( p<0.05 ) found in hand grip isometric muscle strength in total and in gender based , could be linked to the possible association between ppi usage and hypomagnesemia which is related to muscle cramps , something that has been proofed previously by furlanetto & faulhaber and matsuyama et al .
( 31 , 32 ) . when investigating the effect of each of two subgroups of a02b ( ppi and h2ra ) on msh , significantly higher ( p<0.05 ) impact had ppi usage comparing to h2ra , supporting previous findings from vestergaard ( 33 ) .
finally , this study has a couple of limitations , such as the measurement site ( only on distal radial bone ) . while recommendations suggest to perform measurements in hip and lumbar spine as well , due to the lack of accessibility to the device we had to use only distal forearm dxa .
another possible limitation could be the number of participants , but this was mainly due to the type of study , small population of kosova , the small percentage of this age group within this country ( 23.1% ) ( 34 ) , and the difficulties in recruitment process ( the radiological exposure was a big concern amongst our study subjects ) .
the po and popen amongst the mature adults in kosovo seems to be quite low , and together with the relatively high levels of pa ( amongst the study participants ) , allows us to believe that this population stands a solid position against age related msh conditions such as osteoporosis and osteopenia .
nevertheless , future studies using other measurement sites ( such as hip and vertebral region ) should be done in order to prove and establish these results .
one important recommendation resulting from this study would be that the appropriate benefit / risk assessment should be always made before prescribing and ordering medication , while the therapy ordination must be prescribed by qualified health professionals .
one field of particular carefulness should be especially the patients that take medications discussed to be affecting msh for long periods of time , where precautions should always be considered .
this includes recommendation of regular dexa scans , prescription of additional protective therapy , including here bisphosphonates , calcitonin or supplements as calcium - ca , vitamin c or d analogues ( 35 , 36 , 37 ) , as well as prescription of specific physical activity for improving bone health such as multicomponent exercise with an emphasize on resistance exercise ( 38 ) .
it should also be invested in patients awareness raising and medical practitioners professional update , in order for them both to be informed about the positive and negative effects of medicines use and the steps that can be taken to minimize possible side effects .
 background : this observational , cross - sectional study investigates the impact of medication usage , physical activity ( pa ) and nutritional status on musculoskeletal health ( msh ) in males and females aged 40 - 65 in the population of a post conflict , developing country.methods:bone mineral density ( bmd ) , t - score and z - score at distal forearm regions ( measured by dexa scan ) , together with isometric hand grip strength ( dynamometer ) were evaluated in a total of 162 subjects ( 53 males , average age 55.157.12 and 109 females , 54.275.1 ) . 
 additionally , bio - anthropometric assessments , medication usage , pa level and nutritional status were assessed.results:significant differences ( p<0.05 ) were found in total subjects body mass index ( bmi ) , pa , bmd , t - score and hand grip between genders . 
 42% of total participants met the diagnostic criteria of , out of which 6.8% with t - score below -2 , while no cases of osteoporosis was recorded . 
 n05b anxiolytics and a02b drugs for peptic ulcer and gastro - oesophageal reflux disease medication groups consumption turned to have no significant differences ( p>0.05 ) in bmd , t - score , and hand grip in total population , except for a02b where p<0.05 were found in hand grip , as well as between female consumers and no consumers in all variables . 
 meanwhile , in total subjects consuming h02ab glucocorticoids p<0.05 were observed in bmd and t - score , but not on hand grip.conclusions:this study shows a low risk for msh problems amongst the studied population in kosova , while the consumption of h02ab medication group in both genders and a02b in females only for extended periods might effect msh , therefore appropriate benefit / risk assessment should be made before prescribing these medications , notwithstanding age , gender , pa or nutritional status . 