osteoporosis and parkinson s disease ( pd ) are two chronic diseases among many that can lead 
 to a downward spiral in a patient s quality of life , and they particularly affect elderly 
 people .
osteoporosis is a systemic and metabolic skeletal disease characterized by increased 
 risk of bone fragility due to a reduction in bone mass and microarchitectural deterioration 
 of bone tissue1,2,3 .
pd is a chronic , slowly 
 progressive neurodegenerative disease characterized by symptoms of rigidity , 
 akinesia / bradykinesia , resting tremor , postural instability , and gait disorders .
recognized as the second most common neurodegenerative disorder 
 after alzheimer s disease , pd has a great impact on quality of life , as it significantly 
 affects the ability to carry out daily living activities due to both motor and non - motor 
 symptoms and complications of medical treatment5 .
pd patients are at increased risk of falling compared with the 
 general population , since they exhibit progressive symptoms such as reduced arm swing and 
 balance and walking problems , especially at later stages of the disease6 , 7 .
as the risk of 
 fall steps up , falls more frequently occur , and the rates of complications from falls such 
 as fracture increase .
indeed , many studies have revealed that fracture risk , hip fracture 
 being the most common , is increased in patients with pd8,9,10,11 .
osteoporosis - related 
 fractures , especially hip fractures , impair quality of life as the independent mobility 
 level worsens , and ultimately , the patient becomes bed - ridden .
these fractures can lead to 
 death by the end - stage of the disease10 , 12 . considering these potential negative effects ,
the importance of osteoporosis and lower bone 
 mineral density ( bmd ) levels of pd patients are well understood . however , to our knowledge , 
 no studies to date have investigated the bmd , vitamin d levels , and osteoporosis frequency 
 of a pd population by comparing male and female patients with controls separately .
the aim of this study was to compare bmd , vitamin d levels , and osteopenia and osteoporosis 
 rates among male and female patients with pd and controls .
patients aged 5585 years who consecutively admitted to the movement disorders outpatient 
 clinic of our institute between april 2014 and october 2014 were allocated to the study if 
 their medical treatments were optimized , they were diagnosed with pd according to the uk 
 parkinson s disease society brain bank diagnostic criteria13 , and their pd stages were stage 4 or below ; that is , they were 
 still able to walk or stand unassisted or benefited from use of only one mobility aid , as 
 per hoehn and yahr ( h&y ) staging .
patients were excluded if they had a history of any chronic diseases that 
 could affect bone metabolism , had a history of lumbar spine and/or proximal femur fractures , 
 had had an arthroplasty , or had been treated with corticosteroids , antiepileptics , 
 bisphosphonates , hormone replacement therapy or vitamin d replacement therapy in the last 
 year . the participants body mass indices ( kg / cm )
were determined based on 
 demographic data collected from them including their age , gender , height , and weight . 
 following this ,
the properties of pd for each patient , such as disease duration and daily 
 levodopa dosages , were recorded .
in addition , the pd severity scale was determined for each 
 participant based on the h&y classification14 .
unified parkinson s disease rating scale ( updrs ) part iii was 
 utilized to assess the severity of the motor symptoms of pd15 .
if the patients had fluctuations , they were assessed as being in 
 the  on  state , namely  medicine active  .
the control group was formed from individuals who were admitted to the musculoskeletal 
 disorders outpatient clinic of our institute during the study interval .
individuals were 
 excluded if they had a history of metabolic bone disease , had a history of lumbar spine 
 and/or proximal femur fractures , had had an arthroplasty , or had been treated with 
 corticosteroids , antiepileptic , bisphosphonates , hormone replacement therapy or vitamin d 
 replacement therapy in the last year .
the institutional ethics committee of our institute approved the study , and signed informed 
 consent forms were obtained from all participants .
the bmd ( kg / cm ) of the skeletal sites was measured by a trained x - ray 
 technician using a hologic qdr-4500a dual - energy x - ray densitometer ( hologic , bedford , ma , 
 usa ) . the dual - energy x - ray absorptiometry ( dxa ) device was calibrated daily and weekly 
 using the appropriated phantom methods .
measurements were made at the following sites : 
 lumbar spine ( l14 ) , femoral neck , and total hip .
is defined as the number of standard deviations above or below the mean for the 20- to 
 40-year - old healthy adult reference population of the same sex and ethnicity . according to 
 world health organization ( who ) criteria ,
osteopenia is diagnosed when a patient s t - score 
 is between 1.0 and 2.5 standard deviations , and osteoporosis is diagnosed when the t - score 
 is less than or equal to 2.5 standard deviations .
fasting ( at 8.0010.00 a.m. ) 10  cm peripheral venous blood samples were 
 collected from the participants , placed in gel - containing tubes , and then centrifuged at 
 1200 g for 10  min to analyze the serum for 25(oh)d level .
a commercial elisa kit 
 ( immuno - biological laboratories , minneapolis , mn , usa ) was used to measure the serum 25(oh)d 
 level , with the normal range being 11.142.9 ng / ml . a 25(oh)d level below 20
ng / ml was 
 considered to indicate vitamin d deficiency , one between 20 and 30 ng / ml was considered to 
 indicate vitamin d insufficiency , and one higher than 30 ng / ml was considered to be 
 normal .
data were presented as means  standard deviation ( sd ) or counts ( percentages ) .
means were 
 compared using independent t - tests for two groups . statistical significance was based on a 
 5% level .
statistical analyses were performed using medcalc for windows , version 15.6 
 ( medcalc software , ostend , belgium ) .
one hundred fifty - two pd patients were assessed for allocation to the study at the movement 
 disorders clinic over the course of seven months .
a total of 37 patients were excluded from 
 the study ( previously had lumbar surgery and/or total hip replacement surgery ( n=14 ) , 
 previously received a medical treatment on account of osteoporosis diagnosis ( n=19 ) , or 
 previously had deep brain stimulation surgery ( n=4 ) ) .
the study was performed with the 
 remaining 115 pd patients in the pd group and with 117 age- and gender - matched individuals 
 in the control group .
no difference was observed between the pd group and controls according 
 to demographic characteristics ( table 
 1table 1.demographic data for the parkinson s disease patients and controls and clinical 
 characteristics of the parkinson s disease patientssubjectsmalesfemalespd ( n=47)controls ( n=47)pd ( n=68)controls ( n=70)age ( years)67.2  10.2 * 66.8  5.867.1  10.0 * 67.4  6.6weight ( kg)79.1  12.9 * 74.5 
11.771.5  12.7 * 73.9  10.6bmi ( kg / m)28.3  4.0 * 26.9 
4.029.8  5.5 * 31.1  4.4pd : parkinson s disease ; bmi : body mass index . * not significant ) .
pd : parkinson s disease ; bmi : body mass index . * not significant the mean age of pd onset was 67.2  10.2  years for men and 67.1  10.0  years for women .
the 
 mean duration of pd was 85.1  62.6 months for men and 58.5  50.9 months for women .
the 
 mean levodopa dose was 450.5  214.5  mg / day for men and 327.9  326.8  mg / day for women .
the 
 mean updrs part iii score was 16.2  8.4 for men and 17.0  9.6 for women .
table 2table 2.bone mineral density and t - scores of the parkinson s disease patients and 
 controlssubjectsmalesfemalespd ( n=47)controls ( n=47)pd ( n=68)controls ( n=70)lumbar spinebmd ( g / cm)0.986  0.194 * 1.098  0.1700.804  0.132**1.004  0.201t - score0.91  1.750.59  1.372.24  1.17**1.16  1.65femoral neckbmd ( g / cm)0.741  0.128**0.871  0.1480.650  0.123**0.810  0.108t - score2.07  1.18*1.43  1.232.34  1.12**1.36  0.87total femurbmd ( g / cm)0.901  0.148 * 0.995  0.1570.771  0.137**0.929  0.129t - score1.27  1.13*0.54  1.341.69  1.06**0.56  1.09vitamin d ( ng / dl)12.6  7.6**20.6  11.211.7  6.8**18.6  11.4pd : parkinson s disease ; bmd : bone mineral density .
* p<0.05 ; * * p<0.001 shows the mean bmd , t - scores , and vitamin d levels of the pd patients and 
 controls .
the mean bmd was significantly lower in the lumbar spine ( p=0.003 for male , 
 p<0.001 for female ) , femoral neck ( p<0.001 for both ) , and total femur ( p=0.004 for 
 male , p<0.001 for female ) in both male and female pd patients compared with the controls . 

male pd patients femoral neck and total hip t - scores were found to be lower than male 
 controls ( p=0.012 and p=0.005 , respectively ) .
female pd patients also had lower mean 
 t - scores in the lumbar spine , femoral neck , and total femur ( p<0.001 for all ) .
the mean 
 vitamin d levels were significantly lower in both male and female pd patients compared with 
 the controls ( p<0.001 for both ) .
* p<0.05 ; * * p<0.001 the rates of osteopenia and osteoporosis in the lumbar spine , femoral neck , and total hip 
 of male participants were not statistically different compared with the male controls . 

however , the osteopenia and osteoporosis rates in female pd patients in the lumbar spine , 
 femoral neck , and total femur were found to be higher compared with the female controls 
 ( table 3table 3.osteoporosis and osteopenia in parkinson s disease patients and controlssubjectsmalesfemalespd ( n=47)controls ( n=47)pd ( n=68)controls ( n=70)lumbar spine ( n , % ) osteoporosis7 ( 14.9)5 ( 10.6)32 ( 47.1)*15 ( 21.4)osteopenia17 ( 36.2)17 ( 36.2)26 ( 38.2)*33 ( 47.1)normal23 ( 48.9)25 ( 53.2)10 ( 14.7)*22 ( 31.4)femoral neck ( n , % ) osteoporosis14 ( 29.8)7 ( 14.9)39 ( 57.4)**6 ( 8.6)osteopenia24 ( 51.1)29 ( 61.7)19 ( 27.9)**43 ( 61.4)normal9 ( 19.1)11 ( 23.4)10 ( 4.7)**21 ( 30.0)total femur ( n , % ) osteoporosis6 ( 12.8)5 ( 10.6)16 ( 23.5)*10 ( 14.3)osteopenia20 ( 42.6)25 ( 53.2)38 ( 55.9)*32 ( 45.7)normal21 ( 44.7)17 ( 36.2)14 ( 20.6)*28 ( 40.0)vitamin d ( n , % ) deficient42 ( 89.4)*29 ( 61.7)63 ( 92.6)*50 ( 71.4)insufficient2 ( 4.3)*7 ( 14.9)4 ( 5.9)*12 ( 17.1)sufficient3 ( 6.4)*11 ( 23.4)1 ( 1.5)*8 ( 11.4)pd : parkinson s disease . * p<0.05 ; * * p<0.001 ) .
in addition , vitamin d deficiency and insufficiency were identified in 89.4% 
 and 4.3% of the male pd patients and 92.6% and 5.9% of the female pd patients , respectively , 
 which were significantly higher rates than those of their control counterparts ( p=0.008 for 
 male , p=0.004 for female ) ( table 3 ) .
there are three primary outcomes of this study : ( 1 ) lumbar spine , femoral neck , and total 
 hip bmd values were lower in the pd patients group , irrespective of gender , than the control 
 group .
( 2 ) higher rates of osteoporosis and osteopenia of the lumbar spine , femoral neck , 
 and total hip were ascertained in female pd patients by comparison with the controls , 
 whereas a significant difference did not exist for these rates between male pd patients and 
 the controls .
( 3 ) as weighty factors in the development of osteoporosis , lower vitamin d 
 levels and higher rates of vitamin d insufficiency were found for both male and female pd 
 patients in comparison with the controls .
it was also determined that the bmd levels were higher for the men than the women in both 
 the study group and the control group .
it was 
 reported that osteoporosis and osteopenia were present in 91% of female pd patients and 61% 
 of male pd patients and that female patients had 7.3% lower bmd levels than their 
 age - matched controls and concordantly 2.6 times the fracture risk17 , 18 . in women
it has been shown that estrogen can 
 promote apoptosis of bone - resorbing osteoclast and can lead to inhibition of osteoclastic 
 bone resorption19 .
the disappearance of a 
 premenopausal inhibitory effect of estrogen on osteoclastic bone resorption after the 
 postmenopausal stage is a major cause of lower bmd level and higher rates of osteoporosis in 
 women .
immobilization is a leading factor explaining the decreased bone density and the increased 
 risk of osteoporosis in patients with pd . in particular , immobilization becomes more 
 apparent as the ambulation level reduces with pd progression .
besides , restriction of daily 
 living activities in pd patients and transpiring motor symptoms such as bradykinesia , 
 rigidity , postural instability , and gait disturbance form a basis for immobility .
rigidity 
 can be considered to have a positive impact on bmd . on the other hand , that comes to a 
 deadlock
since pd increases muscle weakness and reduces mobility , but decreased mobility 
 increases muscle weakness all the more .
lumbar bmd levels are independently associated with 
 the strength of the trunk muscles rather than trunk rigidity20 , whereas the specific cause of muscle weakness is not known in 
 pd21 , 22 .
bone tissue is sensitive to the mechanical environment that it 
 belongs to ; that is , bone tissue is constantly exposed to mechanical stimulation by muscle 
 contraction and body movement that applies forces to the bone . in response to mechanical 

stresses on the bone tissue , osteocytes stimulate bone remodeling by producing molecular 
 signals stimulating osteoblasts and osteoclasts23 .
subnormal mechanical stress as a result of reduced mobility leads 
 to bone mass loss depending on duration and dosage .
sato 
 et al . analyzed the effect of immobilization - induced hypercalcemia on bone metabolism in pd 
 patients and found that increased serum calcium levels correlated negatively with updrs part 
 iii , suggesting the presence of immobilization - induced bone resorption with resultant 
 hypercalcemia in patients with pd25 . in 
 the present study ,
the bmd values for the femoral region of interest showed greater 
 statistically significant differences than those for the lumbar spine in the pd patients 
 compared with the controls group .
the reason for this might be the decreased downward axial 
 mechanical loading in the femoral region due to decreased mobility26 .
another consideration for low bmd values in pd patients may be hyperhomocysteinemia due to 
 l - dopa treatment .
it has been shown that patients with pd have higher serum homocysteine 
 concentrations than controls , while the serum homocysteine levels were found to be 
 independently associated with the bmd of the proximal femur27 .
homocysteine can induce differentiation of osteoclasts and 
 apoptosis of osteoblasts28,29,30 ; thus , it is 
 rational to infer that pd patients are readily affected by osteoporosis .
vitamin d deficiency is a major cause of lower bmd levels and a higher risk of osteoporosis 
 and osteopenia in pd patients when compared with controls .
the recent studies indicating 
 that pd patients have lower levels of 25(oh)d relative to controls31,32,33 .
it has also been demonstrated that a low vitamin d 
 concentration was associated with bone loss21 .
the prevalence of vitamin d deficiency in pd patients is higher 
 compared with that of patients with alzheimer s disease32 .
this suggests that there is a specific relationship between 
 vitamin d deficiency and pd .
calcitriol ( 1,25(oh)2d ) can be synthesized in neurons and 
 microglia as a means of activating 1-hydroxylase .
it was suggested that sustained 
 inadequate vitamin d intake leads to a chronic loss of dopaminergic neurons and plays an 
 important role in the pathogenesis of pd31 .
vitamin d status is a significant factor of skeletal integrity , and inadequate serum 
 25(oh)d level is correlated with weakness of muscles and increased incidences of falls and 
 related fractures34 .
it can be concluded 
 that vitamin d deficiency in pd patients may result in decreased bmd values and increased 
 risk of osteoporosis .
immobilization - induced hypercalcemia can cause suppression of 
 1,25-(oh)2d in the kidney by partially inhibiting parathyroid hormone 
 secretion25 .
furthermore , sunlight 
 deprivation due to immobilization may also lead to vitamin d deficiency in patients with 
 pd35 .
this study showed that vitamin d 
 levels both in male and female pd patients were lower compared with those of the controls . 

the study elucidates that all pd patients regardless of gender have high vitamin d 
 deficiency and insufficiency rates .
malnutrition is a quite common problem , specifically in patients with an advanced stage of 
 pd .
hand - eye coordination disorders , dysphagia , intestinal hypermotility , depression , 
 cognitive deficits , and the side effects of antiparkinsonian medications increases the risk 
 of malnutrition .
the reduction in bmi due to malnutrition may produce negative effects on 
 bmd in the case of axial loading , although the present study could not observe any 
 differences in bmi for either gender between pd patients and the control group . 

additionally , regarding reduced bmd , a lower body fat content has also been found to be 
 associated with lower estriol secretion in women16 .
also , malnutrition adversely affects the stability of vitamin d , 
 and it results in deficiency of folic acid and vitamin b12 , which leads to increased 
 homocysteine . to the best of our knowledge ,
this is the first case - control study on bmd scores , vitamin d 
 levels , and osteoporosis in pd patients that has separately compared male and female groups 
 with controls .
firstly , h&y stage 5 patients 
 were not included in the study ; that is , the negative impact of stage 5 disease on bmd was 
 avoided . in connection with this ,
higher rates of osteoporosis and osteopenia might have 
 been ruled out . secondly , it was not a population - based study .
therefore , the osteopenia and osteoporosis rates , as well 
 as vitamin d levels , could be different from those of the general population .
thirdly , we 
 did not collect data about dietary habits ( e.g. , smoking , alcohol consumption , or receipt of 
 a vitamin d - fortified diet ) , activities of daily living , and amount of sunlight exposure , 
 which might affect vitamin d levels and bmd scores .
the main finding of this study was that all the pd patients had lower bmd levels , both in 
 the lumbar and femoral regions , compared with the controls regardless of gender .
in 
 addition , the frequency of osteoporosis was only higher in female pd patients . 

consequentially , screening for osteoporosis is needed as part of evaluations of patients 
 diagnosed with pd in order to establish preventive measures to limit the future risk due to 
 osteoporotic fractures , which may reduce qualify of life and even increase mortality .
 [ purpose ] the aim of this study was to determine the bone mineral density , vitamin d 
 level , and frequencies of osteopenia and osteoporosis in patients with parkinson s disease 
 and to compare male and female patients with the controls separately . 
 [ subjects and 
 methods ] one hundred fifteen parkinson s disease patients ( 47 males , 68 females ; age 
 range : 5585  years ) and 117 age- and gender - matched controls ( 47 males , 70 females ) were 
 enrolled in the study . bone mineral density measured by dual - energy x - ray absorptiometry 
 and serum d vitamin levels of each participant 
 were recorded . 
 [ results ] the mean lumbar 
 spine , femur neck , and total femur bone mineral density levels , t - scores , and vitamin d 
 levels were found to be significantly lower in parkinson s disease patients in both 
 genders . 
 furthermore , osteoporosis rates were found be significantly higher only in female 
 parkinson s disease patients compared with female controls . 
 [ conclusion ] data from the 
 present study revealed that while osteoporosis was significantly higher only in female 
 parkinson s disease patients , all parkinson s disease patients had lower bone mineral 
 density scores and vitamin d levels compared with the controls regardless of gender , 
 suggesting that clinicians should pay attention to the osteoporosis risk in parkinson s 
 disease and that adequate preventive measures should be taken in order to limit the future 
 risk due to osteoporotic fractures . 