Important Risk Factor For Osteoporosis Research Articles

Low serum levels of zinc, copper, and iron as risk factors for osteoporosis: a meta-analysis.

Zinc (Zn), copper (Cu), and iron (Fe) are essential trace elements for the growth, development, and maintenance of healthy bones. However, there are conflicting reports as to the relationship between serum level of Zn, Cu, or Fe and osteoporosis (OP). The purpose of the present study is to clarify the relationship between serum Zn, Cu, or Fe and OP using a meta-analysis approach. We searched all articles indexed in PubMed published up to May 2014 concerning the association between serum level of Zn, Cu, or Fe and OP. Eight eligible articles involving 2,188 subjects were identified. Overall, pooled analysis indicated that patients with OP had a lower serum level of Zn, Cu, or Fe than the healthy controls (Zn standardized mean difference (SMD) = -1.396, 95% confidence interval (CI) = [-2.129, -0.663]; Cu SMD = -0.386, 95% CI = [-0.538, -0.234]; Fe SMD = -0.22, 95% CI = [-0.30, -0.13]). Further subgroup analysis found that geographical location and gender had an influence on the serum level of Zn in OP and healthy controls, but not on the serum level of Cu or Fe. No evidence of publication bias was observed. In conclusion, this meta-analysis suggests that low serum levels of Zn, Cu, and Fe seem to be important risk factors for OP and well-designed studies with adequate control for confounding factors are required in future investigations.

AB0814 Cross Sectional Study of Hypovitaminosis D in among Rheumatology Patients in Brunei

BackgroundVitamin D deficiency is increasingly recognised as a global health problem. The important role of vitamin D in skeletal health is well established. Studies have shown vitamin D deficiency in...

Comparative evaluation of serum levels of main minerals and postmenopausal osteoporosis

ObjectiveThe purpose of this study was to determine the relationship between serum main minerals and postmenopausal osteoporosis. Study designA total of 728 postmenopausal women were included in this study. Women were separated into two groups according to presence or absence of osteoporosis (OP). BMD was measured in total femur (TF), femoral neck (FN) and lumbar spine (L1–L4) by dual-energy X-ray absorptiometry. Risk factors for OP were recorded by using a structured questionnaire. Main outcome measuresWomen's blood were collected and serum concentrations of iron, copper, zinc, sodium, potassium, magnesium, calcium, ionized calcium, inorganic phosphorus were measured. ResultsLow serum copper levels were significantly associated with OP according to BMD values for TF, FN and L1–L4. There was a significant relationship between low serum zinc levels and OP for L1–L4 spines. Low iron serum levels were also significantly associated with OP in BMD measurements of TF. Low serum magnesium levels had significant association with OP of L1–L4 spines and TF. Serum levels of calcium, ionized calcium, potassium, sodium and inorganic phosphorus were not associated with OP. ConclusionsIn postmenopausal women, the low serum levels of copper, zinc, iron and magnesium appear to be an important risk factor for OP.

Relationship between bone resorption, oxidative stress and inflammation in severe COPD exacerbation

BackgroundThe natural course of chronic obstructive pulmonary disease (COPD) is complicated by the development of systemic consequences and co-morbidities. Increasing evidence indicates that COPD and osteoporosis are strongly linked. The common features in COPD pathology, history of smoking, age, inactivity, systemic inflammation, and use of systemic corticosteroids, are important risk factors for osteoporosis. MethodsPulmonary function, matrix metalloproteinase, tissue inhibitor of metalloproteinases, oxidative stress parameters, inflammatory markers and bone resorption marker were measured in 85 COPD patients and 47 healthy subjects. In patients, all parameters were assessed at two time points: one day after admission during exacerbation and about 30days after, in the stable state of disease. ResultsIn patients, bone resorption marker collagen type I β-isomerized C-terminal telopeptide (beta CL) was increased during exacerbation: geometric mean 0.521, compared with stable patients 0.408, p<0.01, and control subjects 0.362ng/ml, p<0.001. During exacerbation high sensitivity C-reactive protein (hsCRP) and neutrophil count were significantly higher in COPD patients compared with the control group, p<0.001. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations were significantly higher in COPD patients, stable state or exacerbation, compared with control subjects, p<0.001. In patients during exacerbation, total oxidative status (TOS) was higher compared with the stable state, p<0.05 and control group, p<0.001. Multiple linear regression for the joint influence of inflammation, hypoxia and oxidative status during exacerbation showed almost 60% influence on the variability of beta CL concentrations. ConclusionIntensification of disease characteristic symptoms such as inflammation, hypoxia, protease/antiprotease imbalance and oxidative stress, during exacerbation episodes in COPD patients may also contribute to increased bone resorption.

Bivariate Genome-Wide Association Analyses Identified Genes with Pleiotropic Effects for Femoral Neck Bone Geometry and Age at Menarche

Femoral neck geometric parameters (FNGPs), which include cortical thickness (CT), periosteal diameter (W), buckling ratio (BR), cross-sectional area (CSA), and section modulus (Z), contribute to bone strength and may predict hip fracture risk. Age at menarche (AAM) is an important risk factor for osteoporosis and bone fractures in women. Some FNGPs are genetically correlated with AAM. In this study, we performed a bivariate genome-wide association study (GWAS) to identify new candidate genes responsible for both FNGPs and AAM. In the discovery stage, we tested 760,794 SNPs in 1,728 unrelated Caucasian subject, followed by replication analyses in independent samples of US Caucasians (with 501 subjects) and Chinese (with 826 subjects). We found six SNPs that were associated with FNGPs and AAM. These SNPs are located in three genes (i.e. NRCAM, IDS and LOC148145), suggesting these three genes may co-regulate FNGPs and AAM. Our findings may help improve the understanding of genetic architecture and pathophysiological mechanisms underlying both osteoporosis and AAM.

One year B and D vitamins supplementation improves metabolic bone markers

Vitamin D and vitamin B deficiency are common in elderly subjects and are important risk factors for osteoporosis and age-related diseases. Supplementation with these vitamins is a promising preventative strategy. The objective of this study was to evaluate the effects of vitamins D3 and B supplementation on bone turnover and metabolism in elderly people. Healthy subjects (n=93; >54 years) were randomly assigned to receive either daily vitamin D3 (1200 IU), folic acid (0.5 mg), vitamin B12 (0.5 mg), vitamin B6 (50 mg), and calcium carbonate (456 mg) (group A) or only vitamin D3 plus calcium carbonate (group B) in a double blind trial. We measured at baseline and after 6 and 12 months of supplementation vitamins, metabolites, and bone turnover markers. At baseline mean plasma 25-hydroxy vitamin D [25(OH)D] was low (40 or 30 nmol/L) and parathormone was high (63.7 or 77.9 pg/mL). 25(OH)D and parathormone correlated inversely. S-Adenosyl homocysteine and S-adenosyl methionine correlated with bone alkaline phosphatase, sclerostin, and parathormone. One year vitamin D3 or D3 and B supplementation increased plasma 25(OH)D by median 87.6% (group A) and 133.3% (group B). Parathormone was lowered by median 28.3% (A) and 41.2% (B), bone alkaline phosphatase decreased by 2.8% (A) and 16.2% (B), osteocalin by 37.5% (A) and 49.4% (B), and tartrate-resistant-acid-phosphatase 5b by 6.1% (A) and 36.0% (B). Median total homocysteine (tHcy) was high at baseline (group A: 12.6, group B: 12.3 µmol/L) and decreased by B vitamins (group A) to 8.9 µmol/L (29.4%). tHcy lowering had no additional effect on bone turnover. One year vitamin D3 supplementation with or without B vitamins decreased the bone turnover significantly. Vitamin D3 lowered parathormone. The additional application of B vitamins did not further improve bone turnover. The marked tHcy lowering by B vitamins may modulate the osteoporotic risk.

DNA damage drives accelerated bone aging via an NF-κB–dependent mechanism

Advanced age is one of the most important risk factors for osteoporosis. Accumulation of oxidative DNA damage has been proposed to contribute to age-related deregulation of osteoblastic and osteoclastic cells. Excision repair cross complementary group 1-xeroderma pigmentosum group F (ERCC1-XPF) is an evolutionarily conserved structure-specific endonuclease that is required for multiple DNA repair pathways. Inherited mutations affecting expression of ERCC1-XPF cause a severe progeroid syndrome in humans, including early onset of osteopenia and osteoporosis, or anomalies in skeletal development. Herein, we used progeroid ERCC1-XPF-deficient mice, including Ercc1-null (Ercc1(-/-)) and hypomorphic (Ercc1(-/Δ)) mice, to investigate the mechanism by which DNA damage leads to accelerated bone aging. Compared to their wild-type littermates, both Ercc1(-/-) and Ercc1(-/Δ) mice display severe, progressive osteoporosis caused by reduced bone formation and enhanced osteoclastogenesis. ERCC1 deficiency leads to atrophy of osteoblastic progenitors in the bone marrow stromal cell (BMSC) population. There is increased cellular senescence of BMSCs and osteoblastic cells, as characterized by reduced proliferation, accumulation of DNA damage, and a senescence-associated secretory phenotype (SASP). This leads to enhanced secretion of inflammatory cytokines known to drive osteoclastogenesis, such as interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and receptor activator of NF-κB ligand (RANKL), and thereby induces an inflammatory bone microenvironment favoring osteoclastogenesis. Furthermore, we found that the transcription factor NF-κB is activated in osteoblastic and osteoclastic cells of the Ercc1 mutant mice. Importantly, we demonstrated that haploinsufficiency of the p65 NF-κB subunit partially rescued the osteoporosis phenotype of Ercc1(-/Δ) mice. Finally, pharmacological inhibition of the NF-κB signaling via an I-κB kinase (IKK) inhibitor reversed cellular senescence and SASP in Ercc1(-/Δ) BMSCs. These results demonstrate that DNA damage drives osteoporosis through an NF-κB-dependent mechanism. Therefore, the NF-κB pathway represents a novel therapeutic target to treat aging-related bone disease.

Comment on Sanfélix-Genovés et al.: Prevalence of osteoporotic fracture risk factors and antiosteoporotic treatments in the Valencia region, Spain. The baseline characteristics of the ESOSVAL cohort

Dear Editor, We read with interest the study by Sanfelix-Genoves et al. [1] in Osteoporosis International regarding the prevalence of the most important risk factors for osteoporosis and osteoporotic fracture in a large sample of women and men from the Mediterranean region of Valencia, Spain. The authors report a prevalence of osteoporosis of 30.2 % (95 % CI 28.7–31.6 %) in the women and 6.2 % (95 % CI 5.6–6.8 %) in the men. The prevalence observed in the women is similar to that previously observed by the same group [2] but higher than those reported by Diaz-Curiel et al. [3]. Despite the different rates reported by other local studies, the prevalence observed by Sanfelix-Genoves et al. is the highest observed to date in Spain in such a large sample. Beyond the possibility that there are real differences between populations within Spain (which underscores the importance of population-based studies to assess the real prevalence of osteoporosis), after analyzing their data, we would like to make the following comments:

Prevalence of osteoporotic fracture risk factors and antiosteoporotic treatments in the Valencia region, Spain. The baseline characteristics of the ESOSVAL cohort

This study provides information on the prevalence of the most important risk factors for osteoporosis and osteoporotic fracture in a large sample of women and men from the Valencia region and also provides the FRAX 10-year major and hip fracture risks for this population, as well as data about the use of diagnostic tests and antiosteoporotic treatments. The purpose of this study was to describe demographic characteristics, osteoporosis risk factors, the 10-year risk of osteoporotic fracture, and the use of densitometry and antiosteoporotic treatments in the Valencia region, Spain. A cross-sectional study using the ESOSVAL cohort baseline data was conducted. We analyze the data from 5,310 women and 5,725 men aged 50 and over who attended to 272 collaborating primary care centers in 2009-2010. We collected the demographic, anthropometric, clinical, and pharmacy data from the electronic medical record. The mean age of participants was 64.3 years old for women and 65.6 years old for men. The most frequent fracture risk factors were sedentary life (22.2 %) and previous fracture (15.8 %) in women and low calcium intake (21.4 %) and current smoker (20.9 %) in men. According to FRAX(®), the 10-year risk of presenting a major fracture was 5.5 % for the women and 2.8 % for the men. The 10-year risk for hip fracture was 1.9 and 1.1 % for the women and the men, respectively; 23.8 % of the women and 5.2 % of the men had a densitometry test, 27.7 % of the women and 3.5 % of the men were taking calcium and/or vitamin D supplements, and 28.2 % of the women (22.0 % in the 50-64 age group) and 2.3 % of the men were taking antiosteoporotic drugs. The prevalence of certain fracture risk factors not included in the FRAX tool (sedentary life, falls, low calcium intake) is high. In young women, their low risks estimated by FRAX contrast with the high figures for densitometry testing and treatment.

Influence of vitamin D levels on bone mineral density and osteoporosis

BACKGROUND AND OBJECTIVES:The effects of vitamin D on bone mass remain to be understood. This study was conducted with the objective of evaluating the influence of 25-hydroxyvitamin D (25OHD) levels on bone mineral density (BMD) among Saudi nationals.DESIGN AND SETTING:Cross-sectional study carried out at university hospital from 1 February 2008 to 31 May 2008.SUBJECTS AND METHODS:Healthy Saudi men and women in the peak bone mass (PBM) age group and those aged ≥50 years were recruited from the outpatient department of King Fahd University Hospital, Al Khobar, Saudi Arabia, between February 1, 2008, and May 31, 2008. Patient age and sex were documented, and body mass index was calculated. Hematological, biochemical, and serum 25OHD tests were performed. BMD was determined by dual-energy x-ray absorptiometry of the upper femur and lumbar spine. Patients were divided into three groups, based on their 25OHD level.RESULTS:Data from 400 patients were analyzed. Among individuals with a normal 25OHD level, 50% of women and 7% of men in the PBM age group and 26.4% of women and 49.2% of men aged ≥50 years had low bone mass. In patients with 25OHD insufficiency, 84.2% of women and 88.9% of men in the PBM age group and 83.3% of women and 80% of men aged ≥50 years had low bone mass. Results for patients with 25OHD deficiency revealed that none of the men and women in the PBM age group or ≥50 years old had normal BMD. Significant positive correlations between 25OHD level and BMD and significant negative correlations with parathyroid hormone were shown in most of the groups.CONCLUSIONS:This study showed that the vitamin D level significantly influences BMD reading among Saudi individuals. Evaluation and treatment of hypovitaminosis D should be considered during management of low bone mass.

Low‐level chronic exposure to cadmium enhances the risk of long bone fractures: a study on a female rat model of human lifetime exposure

In the present paper, the hypothesis that low chronic exposure to cadmium (Cd) enhances the risk of long bone fractures was investigated in a female rat model simulating human lifetime exposure in non-Cd-polluted areas. For this purpose, the femur and both tibias of control female rats and those exposed to Cd (1 mg Cd I(-1) in drinking water for 24 months since weaning) were assigned to geometric, densitometric (bone mineral content, BMC, and density, BMD), radiographic and biomechanical studies as well as assessing their chemical composition. The exposure to Cd disturbed mineralization (decreased BMD and minerals content, including calcium, magnesium, zinc, copper and iron) and weakened the biomechanical strength of the femur and tibia, enhancing their fragility. The Z-score values for the BMD revealed osteopenia of the femur and tibia in 20 and 30% of the Cd-exposed female rats, respectively, and osteoporosis in 80 and 70%, respectively. In 30% of the Cd-exposed animals, femoral neck fracture was evident in the radiographic picture. The findings seem to confirm the hypothesis that a low exposure to Cd during the lifetime may be an important risk factor for osteoporosis and fractures of long bones, and especially for femoral neck fracture in elderly women. The results indicate that greater attention should be paid to Cd as an environmental risk factor for the increasing rate of osteoporosis and bone fractures in old population.

Association of vitamin D receptor gene polymorphisms with BMD and their effect on 1, 25-dihydroxy vitamin D3 levels in pre- and postmenopausal South Indian women from Andhra Pradesh

Background Osteoporosis is a multifactorial disorder with a strong genetic component and vitamin D receptor gene has been suggested as a candidate gene for osteoporosis. Therefore the present study was aimed to investigate the role of the VDR Fok 1 gene polymorphism and its influence on vitamin D3 levels and BMD in pre- and postmenopausal osteoporotic women of Indian ethnicity. Methods 427osteoporotic women and 460 age matched controls were included in the study. VDR FOK1 gene polymorphism was assessed by the PCR-RFLP method. Serum vitamin D3 was measured by the HPLC method. Results The frequency of ff genotype and f allele was significantly high in pre- and postmenopausal osteoporotic women in comparison with controls (p < 0.001).In each case individuals with ff genotype had significantly low BMD in comparison with Ff and FF genotypes. No significant association was found between the genotypes and vitamin D3 levels. Conclusion The VDR Fok 1 gene is associated with low bone mass in all our study subjects. The genotype ff of the VDR Fok 1 gene is associated with osteoporosis. Further ff genotype associated significantly with low bone mass. Therefore the f allele of VDR Fok1 gene is an important risk factor for osteoporosis.

Depression, Selective Serotonin Reuptake Inhibitors, and Osteoporosis

An increasing number of studies suggest an association between depression and osteoporosis. In a mouse model, depression induces bone loss, mediated by brain-to-bone sympathetic signaling. Depression and bone antianabolic sympathetic tone are alleviated by increasing central serotonin (5-hydroxytryptamine, 5-HT) levels. However, selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants, increase extracellular 5-HT levels but have deleterious skeletal effects. The skeletal serotonergic system consists of 5-HT receptors and the 5-HT transporter (5-HTT) in osteoblasts and osteocytes. 5-HTT is a transmembrane protein targeted by SSRIs. 5-HT restrains osteoblastic activity, thus leading to bone loss. Apparently, the negative skeletal effects of the peripheral SSRI-induced increase in 5-HT outweighs the skeletal benefits resulting from the enhanced central 5-HT antidepressant and antisympathetic activity. Overall, major depression appears as an important risk factor for osteoporosis. However, antidepressants, mainly SSRIs, should be evaluated in view of the causal relationship between depression and bone loss, and vis-à-vis their skeletal adverse effects. Patients with depressive disorders should undergo a routine skeletal evaluation and receive timely antiosteoporotic therapy, especially when SSRI treatment is prescribed.

Proinflammatory cytokines and osteoporosis

Experimental studies indicate that the proinflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha are important regulators of bone resorption and may play an important role in age- and estrogen deficiency-related bone loss. Although the observation of accelerated bone loss in patients with inflammatory disorders supports this mechanism, the role of cytokines in the etiology of osteoporosis has yet to be determined. Elucidation of this potential relationship could not only provide clinicians with an additional tool to identify patients at risk for osteoporosis, but may also inform the development of cytokine-blocking therapies as potential interventions to curb bone loss. Although some epidemiologic studies suggest increases in proinflammatory cytokines are associated with decreased bone mass and greater fracture risk, the totality of evidence is limited and provides no clear indication of which cytokines may be most important for bone health. Additional studies are required to establish if inflammation is an important risk factor for osteoporosis.

Depression and low bone mineral density: a meta-analysis of epidemiologic studies

The association between depression and loss of bone mineral density (BMD) has been reported inconsistently. This meta-analysis, which pooled results from 14 qualifying individual studies, found that depression was associated with a significantly decreased BMD, with a substantially greater BMD decrease in depressed women and in cases of clinical depression. The reported association between depression and loss of BMD has been controversial. This meta-analysis was conducted to determine whether depression and BMD are associated and to identify the variation in some subgroups. English-language articles published before October 2008 were used as the data source. A total of six case-controlled and eight cross-sectional studies met prestated inclusion criteria (N = 10,523). Information on study design, participant characteristics, measurements of BMD and depression, and control for potential confounders was abstracted independently by two investigators using a standardized protocol. Overall, depression was associated with a significant decrease in mean BMD of spine (-0.053 g/cm(2) [95% confidence interval {CI} -0.087 to -0.018 g/cm(2)]) and hip (-0.052 g/cm(2) [95% CI -0.083 to -0.022 g/cm(2)]). A substantially greater BMD decrease was observed in depressed women (-0.076 g/cm(2) in spine; -0.059 g/cm(2) in hip) and in cases of clinical depression (-0.074 g/cm(2) in spine; -0.080 g/cm(2) in hip). Depression is associated with low BMD, with a substantially greater BMD decrease in depressed women and in cases of clinical depression. Depression should be considered as an important risk factor for osteoporosis.

Poverty is a risk factor for osteoporotic fractures

This study assesses the possible association between poverty and osteoporosis and/or fragility fractures in a population of postmenopausal women. We found that postmenopausal women with low socioeconomic status had lower values of BMD at the lumbar spine, a higher prevalence of densitometric osteoporosis, and a higher prevalence of total and vertebral fractures. Some lifestyles are related to the presence of osteoporosis and/or fragility fractures, whereas poverty is related to some lifestyles. Because of this, we studied the possible association of poverty with osteoporosis and fractures. This was an observational, cross-sectional study performed in the Canary Islands, Spain. Participants consisted of a total of 1,139 ambulatory postmenopausal women aged 50 years or older with no previous osteoporosis diagnosis and who were enrolled in some epidemiological studies. The prevalence of fractures (vertebral and non-vertebral) and the prevalence of osteoporosis (T-score <-2.5 either at the lumbar spine or the femoral neck). A previously validated questionnaire elicited the most important risk factors for osteoporosis: socioeconomic status, defined by the annual income was also assessed by a personal interview. A dorso-lateral X-ray of the spine was performed, and bone mineral density (BMD) was measured by DXA in the lumbar spine (L2-L4) and proximal femur. Compared to women with a medium and high socioeconomic status (n = 665), those who were classified into poverty (annual family income lower than 6,346.80 Euros, in a one-member family, n = 474), were older and heavier and had lower height, lower prevalence of tobacco and alcohol consumption, lower use of HRT and higher use of thiazides. After correcting for age and body mass index (BMI), women in poverty had lower spine BMD values than women with a medium and high socioeconomic status (0.840 g/cm(2) vs. 0.867 g/cm(2), p = 0.005), but there were no statistical differences in femoral neck BMD between groups. The prevalence of osteoporosis was also higher in women in poverty [40.6% vs. 35.6%, (OR 1.35, CI 95%: 1.03; 1.76)] after adjusting by age and BMI. Moreover, 37.8% of women in poverty had a history of at least one fragility fracture compared to 27.7% of women not in poverty (OR: 1.45, CI 95%: 1.11; 1.90). The prevalence of vertebral fractures was also higher in women in poverty 24.7% vs. 13.4%, (OR 2.01, CI 95%: 1.44; 2.81). Postmenopausal women with low socioeconomic status had lower values of BMD at the lumbar spine, and a higher prevalence of densitometric osteoporosis, and a higher prevalence of total and vertebral fractures. Because of this, apart from the well known risk factors for osteoporosis, poverty should be taken into account as a possible risk factor for both osteoporosis and fragility fractures, in order to establish sanitary strategies to protect unfavoured postmenopausal women.

Low bone mineral density and high bone metabolism turnover in premenopausal women with unipolar depression

Introduction and hypothesis The majority of studies reporting decreased bone mineral density (BMD) in patients with unipolar depression neglected sex and age differences and menopause as the most important risk factor for osteoporosis. We presumed that physically healthy premenopausal women with unipolar depression have decreased BMD and altered bone cell metabolism. Methods BMD at lumbar spine and femoral neck by dual X-ray absorptiometry, bone alkaline phosphatase sera activity, 5b-tartarate resistant acid phosphatase sera activity and urine N-terminal telopeptide were measured in 73 premenopausal women with unipolar depression and compared with 47 healthy, age- and osteoporosis risk factors-matched premenopausal women. The duration and severity of depression, hormonal status (cortisol, prolactin, parathormone, oestradiol), antidepressive treatment, and physical activity through whole and modified QUALEFFO-41 questionnaire were evaluated. The results were statistically elaborated by the chi-square test, Student's t-test for independent samples, one-way analysis of variance — ANOVA, one-sample Kolmogorov–Smirnov test. Correlations were assessed by means of Pearson's coefficient. Results Patients with unipolar depression had significantly lower BMD, the decrease of which correlated only with the duration of depression. High bone metabolism turnover was found with a predomination of osteoresorption which, but not osteosynthesis, correlated with the severity of depression, estimated through Hamilton depression scores. Despite higher but not significant levels of cortisol in women with unipolar depression, the BMD decrease and high bone turnover seem not to be the consequence of hormonal changes or medical treatment. The significant correlations between physical activity and osteoresorption markers were found indicating possible underlying mechanism. Conclusions Premenopausal women with unipolar depression have significantly lower BMD because of stimulated bone cell metabolism with predomination of osteoresorption process, mostly due to decreased physical activity in depression. These women should be investigated for osteoporosis and the multidisciplinary team approach is advocated.

Prevalence of Vitamin D Deficiency in Uninsured Women

Vitamin D deficiency, an important risk factor for osteoporosis and other chronic medical conditions, is epidemic in the United States. Uninsured women may be at an even higher risk for vitamin D deficiency than others owing to low intake of dietary and supplemental vitamin D and limited sun exposure. Our goal was to determine the prevalence of vitamin D deficiency in this vulnerable population. We enrolled 145 uninsured women at a County Free Medical Clinic in urban Michigan. Questionnaires were used to obtain information about demographics, medical history, vitamin supplementation, sunlight exposure, and dietary vitamin D intake. The 96 women who were tested for vitamin D status ranged in age from 21 to 65 years (mean 48 +/- 11), and 67% were vitamin D deficient as indicated by a 25-hydroxyvitamin D [25(OH)D)] level <50 nmol/L (20 ng/mL). Non-Caucasians were 3 times more likely than Caucasians to be vitamin D deficient (P = .049). Mean dietary vitamin D intake was low (125 +/- 109 IU/d) and only 24% of the participants used any supplemental vitamin D. Participants with total vitamin D intake <400 IU/day from diet and supplements were 10 times more likely to be vitamin D deficient than others (P < .001). These results demonstrate a high prevalence of vitamin D deficiency in an uninsured, medically underserved female population. Uninsured women should be strongly encouraged to increase their vitamin D intake.

Epidemiology of Osteoporosis

In many countries, including Croatia, there is no disease registry for osteoporosis and osteoporotic fractures. Epidemiological data show that the prevalence of osteoporosis is much higher in Asian people than in white European or North American populations, where the prevalence ranges between 10% and 15%. Epidemiological characteristics of osteoporosis in Croatia are similar to other European countries, though the incidence of osteoporotic fractures is somewhat higher. According to the annual report of registered diseases, the number of patients with osteoporosis and osteoporotic fractures increased during the last 10 years. In 2004, 0.70 % of all registered diseases in Croatia referred to osteoporosis and osteomalacia. The most important risk factors for osteoporosis are age, heredity, lifestyle, chronic diseases, hormonal abnormalities and physical characteristics of bone. Like in other chronic diseases, prevention measures are most important for disease control.

Genomic Regions Identified for BMD in a Large Sample Including Epistatic Interactions and Gender-Specific Effects

A genome-wide linkage scan was conducted using a large white sample to identify QTLs for BMD. We found QTLs in the total sample and the gender-specific subgroups, as well as significant epistatic interactions underlying BMD variations. Low BMD is an important risk factor for osteoporosis and under strong genetic control. To identify quantitative trait loci (QTLs) for regulation of BMD, we performed a large-scale whole genome linkage scan (WGS) involving 4126 individuals from 451 families. In addition to the conventional linkage analyses in the total combined sample of males and females, we conducted epistatic interaction analyses and gender-specific linkage analyses. Significant linkage was detected on 5q23 for wrist BMD (LOD = 3.39) and 15q13 for female spine BMD (LOD = 4.49). For spine BMD, we revealed significant epistatic interactions between 3p25 and 2q32 (p = 0.0022) and between 3p25 and 11q23 (p = 0.0007). We replicated several genomic regions that showed linkage with BMD in previous studies by others and ours, such as 3p21, 1p36, and Xq27. This study highlights the importance of large sample size, incorporation of epistatic interaction, and consideration of gender-specific effects in identifying QTLs for BMD variation. The results of this study provide a foundation for the future fine mapping and gene identification in our population.