bone - density depleting disorders including osteoporosis ( ops ) and osteopenia ( opn ) are age - related disorders characterized by low bone mineral density ( lbmd ) and destruction of bone tissue micro - architecture , resulting in susceptibility to the pathologic fracture ( 1 ) . osteoporosis and opn are commonly expected in postmenopause women over fifty years of age because of hormonal imbalance . bone micro - architecture remodeling is continuous and natural process containing bone resorption and new bone formation . these regular processes also control the calcium homeostasis , and replacement of bone tissue affected by microfractures ( 2 ) . therefore , ops can cause several major skeletal problems , such as pathologic fracture and thereby put at risk the general health . osteoporotic fractures ( vertebral or hip ) as pathologic fractures are associated with significant mortality and morbidity . these complications can affect the health - related quality of life ( hr - qol ) . previous studies showed that hr - qol ( estimated by the sf-36 questionnaire ) was affected two years after vertebral and hip fractures ( 3 ) . low bone density ( lbd ) is one of the most challenging worldwide therapeutic problems , particularly in the developed country ( 2 , 4 ) . different therapeutic agents have been recommended for ops and opn that they purpose to prevent the disease progression or reduce the risk of fractures . calcitonin is an antiresorptive agent , which has been confirmed for the treatment of ops since 2 decades ago ( 5 - 8 ) . calcitonin ( nasal or injection form ) via inhibiting the osteoclastic activity can reduce the risk of osteoporotic fracture . previously , the therapeutic effects of calcitonin on ops and lbd were investigated by using bmd ( 9 ) . this study aimed to evaluate the effect of nasal calcitonin on qol in postmenopause women with lbd . we evaluated postmenopause women who had referred to the general clinic of rheumatology in baqiyatallah university of medical sciences , tehran , iran during a 1-year period between 2009 and 2010 . finally , one hundred and fifteen cases met the inclusion criteria : ( 1 ) bmd at any site of measurement with a t score < -1 sd which is accepted as an international criterion of lbd ( osteopenia ) in postmenopause women ; ( 2 ) no evidence for secondary opn ; ( 3 ) no sufficient response to the pharmacological doses of vitamin d within the past 6 months . patients were overruled if they had present or previous history of nasal polyps or a nasal septal perforation and previous treatment episode with prednisone or other medication which interfering bone metabolism such as estrogen or progesterone , bisphosphonates , and calcitonin . the presence of secondary opn , other bone disorders or other important medical conditions such as hyperparathyroidism , hyperthyroidism , neoplastic disorders and other were left out based on the patient s history , whole body physical examination , routine laboratory tests , and , if necessary , hormone assessment and additional assessment for suspected patients . the patients received 200 iu nasal calcitonin with 2 word brand names ( nasocalcin nasal spray 200 iu , sinadaru , tehran , ir iran and miacalcic 200 iu nasal spray , novartis , uk ) once a day along with calcium tablet ( 1000 mg ) and vitamin d ( 400 iu ) for 6 months . the suspected adverse effects were explained for every participant and all patients were visited every 2 months for adverse effect and efficacy of treatment on clinical manifestation . also , bmd was evaluated by a dual - energy x - ray absorptiometry ( norland company , usa ) at the femoral neck and lumbar spine ( l2 - l4 ) . bone mineral density was assessed at the end of the study on last visit and compared with the baseline . urine and blood samples were collected for the biochemical bone marker assessment at the first and 6 months after the beginning of the treatment . calcium homeostasis was observed by measuring serum and 24-hour urinary calcium and phosphorus levels , parathormone ( pth ) serum levels and serum alkaline phosphatase ( alp ) . other laboratory parameters , which were assessed during the treatment , were as follow : cell blood count , serum calcium , serum phosphorus , creatinine ( cr ) , albumin , blood urea nitrogen ( bun ) , electrolyte ( na and k ) and liver aminotransferases . serum and urine samples were collected on the morning without fasting and avoidance from tobacco . at this clinical survey , a detailed hr - qol questionnaire including the validated persian version of short - form 36 ( sf-36 ) questionnaire was used ( 10 ) . we used the persian version of the sf-36 questionnaire which was extensively evaluated in both reliability and validity base on persian conditions ( 10 - 12 ) . also , the sf-36 has been confirmed under swedish conditions and in several other countries ( 13 - 15 ) . moreover , the quantitative variables distribution was assessed using the kolmogorov - smirnov test and then represented as mean  sd ( standard deviation ) and qualitative variables frequency is presented as a percentage . the paired t - test and pearson correlation were used to compare the impact of calcitonin on the quantitative variables . also , the mantel - hanzel and two - tailed wilcoxon tests were used to compare between qualitative variables and nonparametric variables . finally , linear regression model was used to justify the effect of the confounding factors . spss version 16 ( illinois , usa ) was used to analyze the data and p values  0.05 were considered statistically significant . one hundred and fifteen postmenopause women were included ( age range , 47 - 84 years ) . all patients completed the two steps of the study ( failure to follow : 0% ) . this difference in bmd of lumbar spine was statistically significant but not significant in femur s bmd . c - telopeptide of type i collagen ( ctx ; as a bone resorptive marker ) over the 6-month treatment was decreased significantly ( 3.203  2.24 vs. 2.497  1.657 , p value < 0.001 ) . at the baseline , 55.3% of the patients suffered from low back pain although the frequency of the low back pain during the study changed to 3.5% , 1.8% and 0% , which is statistically significant ( p < 0.001 ) . the 24-hour urine ca level was increased significantly compared to the baseline ( from 216.96  114.68 to 270.87  155.47 , p < 0.001 ) . the 24-hour urine cr level raised from 0.93  0.35 to 1.08  0.37 that this change was significant . moreover , bun at the baseline was 17.08  4.07 and the amount was significantly increased at the end of the study to 18.17  4.35 ( p = 0.043 ) . serum levels of pth , ca , ast , alt and alp total were not changed significantly ( p value > 0.050 ) . also , the changes in femur bmd amount were significantly correlated with weight ( p = 0.014 , r = -0.244 ) and bmi ( p = 0.022 , r = -0.301 ) . at baseline measurement , the total qol score were 88.05  15.63 , and also 6 months after the treatment the sf-36 score was 92.15  13.22 . this difference in hr - qol score was statistically significant ( p < 0.001 ) ( table 2 ) . by using partial correlation , although the probable confounding role of age , age at menopause number of pregnancy , the amount of exercise per day and bmi were adjusted , the difference between baseline and final total score of hr - qol was statistically significant ( p < 0.001 ) . regarding to the univariate test and by using the multivariate analysis , we adjusted the hr - qol score changes regarding to the role of demographic variables . also , changes in the hr - qol score had a significant correlation only with educational level ( p = 0.010 , f = 4.252 , power = 97.5% ) ; however , other demographic characteristics such as age at menopause , age , bmi , number of pregnancy and the amount of exercise per day had no significant correlation with hr - qol ( p > 0.050 ) . changes in hr - qol domains over the 6-month treatment period are presented in table 3 . changes in hr - qol domains only in general health ( gh ) and the short form 36 health survey ( sf-36 ) were not statistically significant ( 0.309 and 0.917 , respectively ) . by using the linear regression model , all of the hr - qol s domains changed significantly compared to the changes in total hr - qol score ( p < 0.001 ) and also affected by other domains . table 4 demonstrates the median change in sf-36 score over follow - up for each domain according to its correlation with together and it seems that mental health ( mh ) was the most effective item , which affected the total sf-36 score change ( p < 0.001 , t = 26.13 ) . abbreviations : bp , bodily pain ; gh , general health ; mh , mental health ; pf , physical function ; er , emotional role functioning ; p , p value ; r , correlation coefficient ; rp , physical role functioning ; sf , social function ; vt , vitality .   statistically significant . the changes in hr - qol domains score during the study were assessed according to the bmd changes and we found that only t - score of spine s bmd and total t - score s changes were significantly correlated with the hr - qol total score changes ( p = 0.003 and p = 0.028 , respectively ) . by using the multivariate analysis , we adjusted the changes in the score of hr - qol domains regarding to the role of demographic variables and we found that only changes in mh score were significantly correlated with total bmd score changes ( p = 0.037 ) , bp score was significantly correlated with bmi ( p = 0.049 ) and rp score was also significantly correlated with bmi and age at menopause ( p = 0.009 and p = 0.013 , respectively ) . osteoporosis and the decrease in bmd is a major health problem throughout the world and its prevalence is increasing especially in developed countries because of increasing in the community age ( 16 ) . osteoporosis is the main cause of pathologic hip and vertebral fractures in elderly ( 17 ) . also , ops and decrease in bone mass can increase mortality and morbidity rate substantially ( 1 , 17 , 18 ) . previous study demonstrated that the osteoporotic cases have lower qol due to limitation in physical activity , chronic mild pain and etc . in spite of the comorbidity and fracture , individuals who affected by lower bone density had poorer qol ( 19 ) . the preventive , analgesic and therapeutic impact of nasal calcitonin on the spinal fracture and therefore back pain in the osteoporosis was declared ( 20 ) . also , qol improvement ( regarding to the improvement in spine bmd ) was coordinated by significant reduction in the frequency of low back pain , which is match with previous reports in osteoporotic patients without the obvious bone fracture ( 21 ) . therefore , it is expected that an effective treatment protocol can improve the hr - qol of these patients . calcitonin is bone resorptive inhibitors , which has approved for treatment of osteoporosis , low bone density and other disorder involving increased bone turnover since 25 years ago . the present study is the first from iran to assess the effectiveness of nasal calcitonin on hr - qol in osteopenic postmenopause women . however , the present study showed a raise in spine bmd more than femoral bmd that this is similar to previous trial studies . also , bmd by dual - energy x - ray absorptiometry ( dxa ) is a reliable method for tracking the response to treatment in patients with ops . changes in bmd score when appear that the bone density be increased at least 3 - 5% from the baseline ( 22 ) . alike confirmed the efficacy of 200 iu daily intranasal calcitonin on improvement of lumbar bmd ( 7 ) . however , we found that changes in the spine t - score were correlated with changes in the total hr - qol score , especially mh . in addition , patients with higher grades of spinal bone density loss showed lower qol score , recommending that the results of vertebral fracture are related to qol ( 23 ) . also , regarding to the findings , mh was most effective domain , which significantly influenced the total score of hr - qol . by contract , dennison et al . demonstrated that in osteoporotic women , mh , sf and re are related with total femur bone density ( 19 ) . also , the mh field is that most of the other areas are affected by confounding factors and it is important to consider all characteristics before interpreting the changes ( 19 ) . moreover , mh was considered as major domain of hr - qol compared to other domains for predicting the qol worsening in progression of bone density loss ( 24 ) . moreover , femoral neck bmd changes were significantly correlated with bmi and weight and in the other hand physical activity and somatic - related domain of hr - qol such as bp and rp were correlated with bmi ; however , they were not significantly correlated with femoral bmd score changes . according to our findings , previous studies confirmed that exercise provide modest benefits for post - menopaus women with opn such as increasing in bmd and also improved the hr - qol of these patients ( 25 ) . overall , it can be assumed that mental health - related qol are more likely related with spinal bmd changes and physical health - related qol domains are more likely related with femoral neck bmd changes . in contrast , dennison et al . demonstrated that they have not found any relationships between the lumbar spine bone loss rate and hr - qol in any domain . previously , calcitonin has been certified for treatment of symptomatic ops although the recent studies clarified the efficacy of nasal form of calcitonin ( 26 , 27 ) . in this study bodily pain and physical role functioning ( pr ) had significant changes over the 6-month treatment period with calcitonin , which these findings are consistent with each other . level of education was identified as an effective factor on the progression of ops and response to the treatment according to the bmd improvement and in this study , educational status was correlated with hr - qol changes ( 28 ) . education can enhance the patients insight and improve the life style and thus assist to the plan of therapy . also , in the present study , we found that bmd t - score of femoral neck was significantly associated with weight and bmi , which it is relatively supported by the previous studies ( 23 , 28 ) . the limitation of this study was short - term duration of follow - up and we have not observed long - term effects of nasal calcitonin on hr - qol . moreover , we did not have a control group to exclude the role of race or nationality although no patients had past history of psychiatric disorders . finally , to confirm the analgesic role of nasal calcitonin on the back pain and also qol in nonfractured opn , we recommend using a quantitative scale such as visual analogue scale ( vas ) along with the qol questionnaire . according to the results of this study , it seems intranasal calcitonin can effectively improve qol of women with low bone density via improving in bone density and bmd and also decreasing bone turnover . furthermore , it seems that hr - qol changes were not influenced by demographic or clinical characteristics .
background : physical activity and mental health could be affected by osteoporosis and various therapeutic options such as calcitonin may influence quality of life ( qol ) of these patients with low bone density ( lbd).objectives : this study aimed to evaluate the effect of nasal calcitonin on qol in post menopause women with lbd.patients and methods : this clinical trial study was performed on one hundred and fifteen menopause women with lbd less than 1 sd in bone mineral densitometry ( bmd ) referred to baqiyatallah hospital in tehran , iran , during 2009 - 2010 . 
 they were assigned to receive 200 iu calcitonin nasal spray along with calcium ( 1000 mg ) and vitamin d ( 400 iu ) for 6 months . 
 quality of life was assessed by short - form 36 ( sf-36 ) questionnaire ( persian - validated version).results : the mean age (  sd ) of the participants was 58.75  8.15 years . 
 intranasal spray of calcitonin increased qol scores significantly ( 88.05  15.63 vs. 92.15  13.22 , p value = 0.000 ) . 
 bone mineral density of spine was increased from 0.834  0.11 to 0.12  0.852 and this difference in bmd of lumbar spine was statistically significant ( p value : 0.003 ) but not significant in femur s bmd ( p value = 0.061 ) . in comparison with bmd indexes , the qol scores especially mental health domain changes had only a significant correlation with the changes of total t score in bmd ( p = 0.031 , coefficient correlation = 0.248).conclusions : it seems that nasal spray of calcitonin can effectively improve qol of women with lbd and qol changes were not influenced by clinical or para - clinical alteration . 
 mental health domain must be more considered in further studies as a predicting domain for health - related quality of life ( hr - qol ) changes .