Bone Mineral Density In Men Research Articles

The relationship between body composition and bone mineral density in men with type 2 diabetes mellitus

The relationship between body composition and bone mineral density in men with type 2 diabetes mellitus

Associations between amino acids and bone mineral density in men with idiopathic osteoporosis

Idiopathic osteoporosis in middle-aged men is characterized by low-level bone formation. Inhibited anabolism may be involved in the pathogenesis of the disease and amino acids may be of importance. In the present study fasting amino acid profiles in plasma and erythrocytes were determined in 22 male idiopathic osteoporosis (MIO) patients and in 20 age-matched healthy men and associated with bone mineral density, bone histomorphometry and hormones. The osteoporotic patients had normal plasma essential amino acids but increased non-essential amino acids ( p = 0.001), particularly glutamine and glycine. The ratio essential/non-essential amino acids, an index of protein nutritional status, was decreased in the MIO patients (0.59 (0.04) μmol/l, mean (SD)), compared to controls (0.66 (0.05), p = 0.001). In the MIO patients, the ratio essential/non-essential plasma amino acids ( r = 0.60, p = 0.003) was positively correlated with lumbar spine bone mineral density. The erythrocyte amino acids represent a large proportion of the free amino acids in blood. A novel finding was the lower levels of erythrocyte tryptophan in MIO (12 (2) μmol/l) compared to controls (16 (3), p = 0.001) and decreased erythrocyte/plasma ratio (0.28 (0.07) vs. 0.33, (0.06), p < 0.01), suggesting an altered amino acid transport of tryptophan between plasma and erythrocytes. In the combined group of MIO and control men ( n = 42), bone mineral density was positively correlated with erythrocyte tryptophan in both the lumbar spine ( r = 0.45, p = 0.003) and femoral neck ( r = 0.56, p < 0.001). The bone histomorphometric variables wall thickness, trabecular thickness and mineral apposition rate were all positively associated with erythrocyte tryptophan levels in the MIO patients. In the combined group of MIO and controls, a multiple regression analysis showed that erythrocyte tryptophan could explain 22% of the variation of lumbar spine and 30% of the variation in femoral neck bone mineral density. We conclude that men with idiopathic osteoporosis have changes in free amino acid profiles which indicate their altered utilization. The correlations between tryptophan and bone mineral density and bone histomorphometry suggest a link between tryptophan and osteoblast function which may be important for bone health.

Effect of Zoledronic Acid on Bone Mineral Density in Men with Prostate Cancer Receiving Gonadotropin-Releasing Hormone Analog

Background. Loss of bone density with androgen deprivation therapy for prostate cancer is well recognized. We assessed the effects of quarterly infusion of zoledronic acid on bone mineral density (BMD) and markers of bone turnover over a one-year period in men receiving gonadotropin-releasing hormone analog (GnRH-a) for prostate cancer. Methods. 41 subjects were randomly assigned to treatment with zoledronic acid (4 mg) IV infusion or placebo every 3 months. The primary endpoint was the change in the lumbar spine BMD after 12 months of treatment. Results. The change in vertebral BMD in the zoledronic acid group (+7.93 ± 1.4%) was significantly (P < .05) greater than the change in the placebo group (+0.82 ± 1.7%) as was the change in left femoral neck BMD (+5.05 ± 1.4% for the zoledronic acid group versus −0.48 ± 1.4% for the placebo group). The decrease in biochemical markers of bone turnover was significantly (P < .05) greater in the zoledronic acid group compared to the placebo group. Conclusion. Quarterly infusion of zoledronic acid for 1 year improved vertebral and left femoral neck BMD with a decrease in bone turnover markers in men on GnRH-a treatment. Zoledronic acid treatment appears to be promising in men with low BMD receiving GnRH-a treatment.

ORIGINAL ARTICLE: The association between serum thyrotropin (TSH) levels and bone mineral density in healthy euthyroid men

SummaryObjective Although osteoporosis is increasingly shown to occur in a considerable proportion of men, data on risk factors for male osteoporosis are limited. In this study, we investigated the association between serum thyrotropin (TSH) concentration and bone mineral density (BMD) in healthy euthyroid men.Design A cross‐sectional community (health promotion centre)‐based survey.Subjects and measurements For 1478 apparently healthy euthyroid men who participated in a routine health screening examination, we measured BMD at the lumbar spine and femoral neck using dual energy X‐ray absorptiometry and serum TSH concentrations using immunoluminometry.Results Lumbar spine BMD linearly increased with TSH level after adjustment for age, weight and height (P for trend = 0·002), and statistical significance persisted after additional adjustment for smoking and drinking habits (P for trend = 0·010). When serum alkaline phosphatase was added as a confounding variable, the relationship was still significant (P for trend = 0·016). Femoral neck BMD also tended to increase in higher TSH concentration after adjustment for age, weight and height (P for trend = 0·042), but this association disappeared after additional adjustment for smoking and drinking habits. The odds of lower BMD (i.e. osteopaenia and osteoporosis combined) were significantly increased in subjects with low‐normal TSH (i.e. 0·4–1·2 mU/l), when compared to high‐normal TSH (i.e. 3·1–5·0 mU/l), after adjustment for confounding factors (odds ratio = 1·45, 95% CI = 1·02–2·10).Conclusion These results suggest that a serum TSH concentration at the lower end of the reference range may be associated with low BMD in men.

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) > or = 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMD(a)) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (beta = 1.83, p = .004) and CTX-I (beta = 17.59, p = 4.74 x 10(-4)), and lower lumbar spine BMD(a) (beta = -0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (beta = -1.84, p = .003) and CTX-I (beta = -27.02, p = 6.06 x 10(-8)) and higher ultrasound BMD at the calcaneus (beta = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men.

Relationship Between Visceral Adiposity and Bone Mineral Density in Korean Adults

The objective of the study was to investigate the relationship between visceral and subcutaneous adiposity measured by computed tomography and bone mineral density (BMD) and to identify the metabolic factors associated with BMD. We studied 461 subjects recruited from the health-care center at Severance Hospital, Yonsei University College of Medicine. Multivariate regression analyses were conducted to examine the cross-sectional associations between body composition-related or metabolic parameters and BMD. After adjusting for body weight and other confounders, visceral fat area had an inverse association with BMD in men (beta = -0.133, P = 0.049 for lumbar spine; beta = -0.135, P = 0.037 for femoral neck; beta = -0.179, P = 0.005 for total hip) and women (beta = -0.424, P < 0.001 for lumbar spine; beta = -0.302, P = 0.005 for femoral neck; beta = -0.274, P = 0.014 for total hip). However, the subcutaneous fat area showed no statistically significant relationship with BMD at most sites. Among the metabolic parameters, HDL cholesterol was positively associated with BMD, while LDL cholesterol was negatively associated with BMD in men. In women, total and LDL cholesterol were negatively associated with BMD at the lumbar spine. We conclude that visceral adiposity is inversely associated with BMD after adjusting for confounders and that metabolic factors may partly contribute to this inverse relation.

Variants at the Znf365 locus are associated with femoral neck bone mineral density in men

Variants at the Znf365 locus are associated with femoral neck bone mineral density in men

Adiponectin and Peak Bone Mass in Men: A Cross-Sectional, Population-Based Study

Adiponectin, a protein classically known to be secreted by adipocytes, is also secreted by bone-forming cells. Results of previous studies have been contradictory as to whether serum adiponectin and bone mineral density (BMD) are associated. The aim of this study was to investigate a possible association between serum adiponectin and BMD in young, healthy men at a time of peak bone mass. BMD in the femoral neck, total hip, and lumbar spine were measured in this population-based cross-sectional study of 700 men aged 20-29 years participating in the Odense Androgen Study. Magnetic resonance imaging of femoral cortical thickness and bone marrow size was performed in a subsample of 363 participants. The associations between serum adiponectin and various bone measures were investigated by means of regression analyses with adjustment for potential confounding variables. An inverse association was found between serum adiponectin and total hip BMD and a direct between adiponectin and femoral bone marrow size (r = -0.092; P = 0.036 and r = 0.164; P = 0.003, respectively). Femoral muscle size may, at least in part, explain the association between adiponectin and total hip BMD. Serum adiponectin was inversely associated with total hip BMD in men at the time of peak bone mass, but this association may be explained by factors related to muscle size and function. The observed association between adiponectin and femoral bone marrow size was retained even after adjustment for potential covariates.

Association between socioeconomic status and bone mineral density in adults: a systematic review

For most causes of mortality and morbidity, a socioeconomic gradient exists; however, this systematic review identified limited evidence for the role of education on bone mineral density (BMD). Further research is required to build upon the current paucity of data examining influences of socioeconomic status (SES) on BMD, especially in men. For most causes of mortality and morbidity, a socioeconomic gradient exists, although little is understood of the relationship between BMD and SES. We systematically evaluated evidence of SES as a risk factor for low BMD at the clinically relevant sites of hip and spine in adults. We conducted a computer-aided search of Medline, EMBASE, CINAHL, and PsychINFO from January 1, 1966 until December 31, 2008. Reviewed studies investigated the relationship between SES parameters of income, education, and occupation, and the level of BMD. Studies were rated based on their methodological quality, and a best-evidence synthesis was used to summarise the results. One case-control and seven cross-sectional studies were identified for inclusion, of which four cross-sectional studies were high-quality. Best-evidence analysis identified consistent, yet limited, evidence for a positive association between educational attainment and BMD in women. No evidence was available regarding an association between income or occupation and BMD in either gender, or education and BMD in men. Limited good quality evidence exists for the role that education level may play in BMD levels. Cohort studies are required to examine the relationship between individual SES parameters and BMD in order to identify potential intervention targets.

Using the same bone density reference database for men and women provides a simpler estimation of fracture risk

Although low bone mineral density (BMD) predicts fractures, there are postulated sex differences in the fracture "threshold." Some studies demonstrate a higher mean BMD for men with fractures than for women, whereas others note similar absolute risk at the same level of BMD. Our objective was to test the preceding observations in the population-based Canadian Multicentre Osteoporosis Study (CaMOS). We included participants 50+ years of age at baseline. Mean BMD in men was higher than in women among both fracture cases and noncases. Three methods of BMD normalization were compared in age-adjusted Cox proportional hazards models. In a model using the same reference population mean and standard deviation (SD), there were strong effects of age and total-hip BMD for prediction of fractures but no significant effect of sex [hazard ratio (HR) = 0.97, 95% confidence interval (CI) 0.78-1.20] for men versus women. In a model using sex-specific reference means but a common SD, an apparent sex difference emerged (HR = 0.66, 95% CI 0.54-0.81) for men versus women. The sex term in the second model counterbalanced the higher risk introduced by the lower normalized BMD in men. A third model using sex-specific reference means and SDs gave nearly identical results. Parallel results for the three methods of normalization were seen when adjusting for clinical risk factors, excluding antiresorptive users and considering death as a competing risk. We conclude that no adjustment for sex is necessary when using common reference data for both men and women, whereas using sex-specific reference data requires a substantial secondary adjustment for sex.

Negative Association between Metabolic Syndrome and Bone Mineral Density in Koreans, Especially in Men

Cardiovascular disease and osteoporosis are thought to share common risk factors, and metabolic syndrome (MS) is composed of major risk factors for cardiovascular disease. This study was performed to investigate the relationships between specific MS components and bone mineral density (BMD). BMD was measured at the femoral neck of Korean men aged 40 years or more (n = 1,780) and postmenopausal women (n = 1,108) using dual-energy X-ray absorptiometry. We identified subjects with MS as defined by two criteria, International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI). Body fat and lean mass were measured via bioimpedance analysis. The prevalence of MS was 19.8% and 7.7% in men and 20.8% and 11.6% in postmenopausal women according to the AHA/NHLBI definition and the IDF definition, respectively. After multivariate adjustment, femoral neck BMD was significantly lower in subjects with MS regardless of diagnostic criteria. BMD decreased as the number of MS components increased (P < 0.001 for trends in both sexes). Among MS components, waist circumference was the most important factor in this negative association. When multiple linear regression models were applied to each 5-kg weight stratum to test for a linear trend, waist circumference and fat mass were negatively associated with BMD and lean mass was positively associated with BMD in men but not in women. MS was associated with a lower BMD in Korean men and postmenopausal women, suggesting that visceral fat may lead to bone loss, especially in men.

Bone and Men's Health. Association between serum testosterone and bone mineral density in patients with diabetes

Osteoporosis in elderly men as well as women is increasingly recognized and patients with type 2 diabetes mellitus have higher risk of fracture than nondiabetic subjects. The relationships between bone stiffness and serum bioavailable testosterone concentrations as well as other variables including age, duration of diabetes, glycemic control (HbA(1c)) , or body mass index were evaluated in 294 men with type 2 diabetes. An inverse correlation was found between stiffness index and age. A positive correlation was found between stiffness index and serum bioavailable testosterone concentration (r = 0.231, p = 0.0005) . Stiffness index was significantly less in current smoker than in past smoker or nonsmoker. No significant correlations were found between stiffness index and duration of diabetes, HbA(1c), or body mass index. In conclusion, serum testosterone concentration is an important factor for bone mineral density in men with type 2 diabetes.

Bone health and prostate cancer.

Bone metastases are a substantial burden to men with advanced prostate cancer as they often cause pain and can cause fractures and spinal cord compression. Osteoblasts and osteoclasts are both pathologically activated in the setting of prostate cancer bone metastases. As osteoclast activation is associated with disease progression, skeletal complications and death, osteoclast-targeted therapies are a rational approach to disease management. Zoledronic acid is standard of care for castration-resistant prostate cancer with bone metastases as it reduces the risk for skeletal-related events. Additional trials are needed to better define the ideal dose, frequency and duration of zoledronic acid therapy. No bisphosphonate has yet been shown to prevent bone metastases or to benefit men with androgen-sensitive disease. Denosumab is an experimental osteoclast-targeted monoclonal antibody against receptor activator of nuclear factor-kappaB ligand. Two ongoing phase III trials are expected to define its efficacy in preventing bone metastases and disease-related skeletal events in men with prostate cancer. Androgen-deprivation therapy (ADT) for prostate cancer is associated with osteoporosis and fragility fractures. Several bisphosphonates have been shown to improve bone mineral density in men receiving ADT. Two recent phase III trials have shown that denosumab and toremifene reduce the incidence of fragility fractures in these men. The World Health Organization has developed a fracture risk assessment model (FRAX) for the general population to guide the selection of patients who may benefit from pharmacotherapy. In the absence of a prostate cancer-specific algorithm, we advocate the use of FRAX for men receiving ADT.

Effects of Denosumab on Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

In a recently completed 3-year, randomized, double-blind study, denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor kappaB ligand, significantly increased bone mineral density and decreased new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. We conducted subgroup analyses to evaluate the relationships between subject characteristics and the effects of denosumab on bone mineral density at multiple skeletal sites. A total of 1,468 subjects were randomized 1:1 to receive 60 mg subcutaneous denosumab every 6 months or placebo for 36 months. In these analyses we evaluated the effects of denosumab on bone mineral density at the lumbar spine, total hip and distal 1/3 radius (substudy of 309 subjects) during 36 months in specific subgroups according to age, duration and type of prior androgen deprivation therapy, bone mineral density T score, weight, body mass index, bone turnover marker levels and prevalent vertebral fractures. After 36 months denosumab significantly increased bone mineral density of the lumbar spine, total hip and distal 1/3 radius by 7.9%, 5.7% and 6.9%, respectively, compared with placebo (p <0.0001 for each comparison). Denosumab significantly increased bone mineral density to a degree similar to that observed in the overall analysis for every subgroup including older men as well as those with prevalent fractures, lower baseline bone mineral density, and higher serum C-telopeptide and tartrate-resistant alkaline phosphatase 5b. Mean increases in bone mineral density at each skeletal site were greatest for men with the highest levels of serum C-telopeptide and tartrate-resistant alkaline phosphatase 5b. Denosumab significantly and consistently increased bone mineral density at all skeletal sites and in every subgroup, including men at greatest risk for bone loss and fractures.

Low Serum Level of the Endogenous Secretory Receptor for Advanced Glycation End Products (esRAGE) Is a Risk Factor for Prevalent Vertebral Fractures Independent of Bone Mineral Density in Patients With Type 2 Diabetes

OBJECTIVEPatients with type 2 diabetes are known to have an increased risk for fracture compared with non–type 2 diabetic control subjects, despite having higher bone mineral density (BMD). We previously showed that serum pentosidine, one of the advanced glycation end products (AGEs), was associated with prevalent vertebral fractures (VFs) in those with type 2 diabetes. The involvement of the endogenous secretory receptor for AGEs (esRAGE) in VFs in those with type 2 diabetes, however, is still unknown.RESEARCH DESIGN AND METHODSWe compared parameters including esRAGE, pentosidine, and BMD in Japanese type 2 diabetic patients (137 men >50 years old and 140 postmenopausal women) with and without VFs.RESULTSThe esRAGE-to-pentosidine ratio in type 2 diabetic patients with VFs was significantly lower than in those without VFs (men: 7.1 ± 2.8 vs. 9.4 ± 6.2, P = 0.013, respectively; women: 4.7 ± 2.7 vs. 8.2 ± 5.4, P < 0.001, respectively). Multivariate logistic regression analysis adjusted for age, BMI, A1C, serum creatinine, duration of diabetes, therapeutic agents, diabetes complications, osteoporotic risk factors, and lumbar BMD identified the serum esRAGE level and esRAGE-to-pentosidine ratio as factors associated with the presence of VFs, independent of BMD in men (odds ratio [OR] 0.46 [95% CI 0.25–0.84], P = 0.012; and OR 0.34 [0.15–0.76], P = 0.009, respectively) and in women (OR 0.32 [0.16–0.67], P = 0.002; and OR 0.14 [0.04–0.43], P = 0.001, respectively).CONCLUSIONSThese results show that serum esRAGE level and esRAGE-to-pentosidine ratio are more useful than BMD for assessing the risk of VFs in type 2 diabetic patients.

Dihydrotestosterone is a determinant of calcaneal bone mineral density in men

Male osteoporosis is an increasingly important health problem worldwide. Though androgen deficiency leads to bone loss in men, information on the relative contribution of aromatizable and non-aromatizable androgens in maintaining bone mineral density (BMD) and the mechanisms involved are unclear. This cross-sectional study was designed to explore the same. Hundred osteoporotic men with age matched normal were studied for serum levels of sex steroids, PTH, IGF system components, cytokines and bone turnover markers. Our findings show that serum DHT, IGF-I, IGF-II and IGFBP-3 levels were significantly decreased while IL-1β and bone turnover markers were significantly increased in osteoporotic men compared to normal. Pearson correlation analysis revealed that serum DHT, IGF-I, IGF-II and IGFBP-3 levels were positively and strongly correlated with BMD, while serum IL-1β levels were negatively correlated with BMD. Serum PTH, testosterone, estradiol, IGFBP-4, TNF-α, IL-4 and IFN-γ levels were similar between the two groups. We observed that DHT levels significantly declined with age. However, the significant difference in DHT between the osteoporotic and normal groups is the same regardless of age. A multiple regression model adjusted for age demonstrated that DHT/BMD association is fairly stronger among those with osteoporosis than the normal. Our findings for the first time point out that DHT is an important determinant of BMD in men. Most importantly, the strong positive correlation of serum DHT with BMD offers new perspectives in understanding the role of non-aromatizable androgen in regulating bone metabolism in men, and might serve as a potential clinical marker in the diagnosis of male osteoporosis.

Risk factors for hip fracture in older adults: a case–control study in Taiwan

We conducted a matched case-control study of hip fracture in older adults. Our findings suggest that hip fracture risk was determined by multiple factors. Older women characterized by low consumption of milk, peak flow rate, grip strength, and bone mineral density (BMD) had increased risk of hip fracture. Older men with impaired cognitive function and low BMD were also at higher risk of hip fracture. Multiple factors contribute to low-trauma hip fracture in older adults. The aim of this study was to determine important characteristics of hip fracture in older population. A total of 228 patients with first low-trauma hip fracture were matched with 497 controls. All 77 potential risk factors of hip fracture organized into 13 groups were analyzed using conditional logistic regression. Low milk intake, peak flow rate, hand grip strength, and bone mineral density in women and low mini-mental state examination score and bone mineral density in men were further identified to be independently associated with elevated hip fracture risk. The factors found in our study may help understand the etiology of hip fracture and be further adopted to evaluate the risk of hip fracture in community and clinical setting.

Association of Luteinizing Hormone Receptor Polymorphism with Bone Mineral Density in Men – Results from Odense Androgen Study

Association of Luteinizing Hormone Receptor Polymorphism with Bone Mineral Density in Men – Results from Odense Androgen Study

The relationship between adipokines, body composition, and bone density in men with chronic obstructive pulmonary disease

Osteoporosis is common in patients with chronic obstructive pulmonary disease (COPD). Data regarding the relationship between adipokines and bone mineral density (BMD) in this population is lacking. The purpose of this pilot study was to determine associations between the adipokines tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin and resistin, body composition, and BMD in men with severe COPD. This was a cross-sectional study of men with severe COPD who visited the University of Colorado Hospital COPD Center. Bone density and parameters of body composition were measured by dual-energy X-ray absorptiometry. Twenty-three men were included (mean age = 66 years, mean percent predicted forced expiratory volume in one second = 32%). On bivariate analysis, there was no association between TNF-alpha and BMD. Parameters of body composition and serum concentrations of leptin and adiponectin were significantly associated with total hip and spine bone density. However, with partial correlation analysis, total body mass was the only independent predictor of total hip BMD, explaining approximately 50% of the variability. Overall, 18 out of 23 men enrolled (78%) had low bone density by T-score, and nine (39%) were classified as having osteoporosis. The men with osteoporosis had lower parameters of body composition, lower mean serum leptin concentrations, and a greater impairment in measures of lung function compared to the men without osteoporosis. We conclude that the effect of adipokines on BMD does not appear to be independent of body mass. However, larger studies are needed to further evaluate the relationship between adipokines, body weight, and BMD in patients with COPD.

Spotlight on Teriparatide in Osteoporosis†

Recombinant teriparatide (Forteo; Forsteo) is an anabolic (bone-forming) agent. Studies have shown that subcutaneous teriparatide 20 microg/day is effective in women with postmenopausal osteoporosis, men with idiopathic or hypogonadal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Teriparatide improves bone mineral density (BMD) and alters the levels of bone formation and resorption markers; histomorphometric studies have shown teriparatide-induced effects on bone structure, strength, and quality. Subcutaneous teriparatide 20 microg/day administered over a treatment period of 11-21 months was effective in reducing the risk of fractures and improving BMD in men with idiopathic or hypogonadal osteoporosis, women with postmenopausal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Furthermore, the beneficial effects of teriparatide on vertebral fracture prevention and BMD appear to persist following treatment cessation. Teriparatide is generally well tolerated and treatment compliance rates are favorable. However, current limitations on the length of treatment and the high acquisition cost mean that teriparatide is best reserved for the treatment of patients with osteoporosis at high risk of fracture, or for patients with osteoporosis who have unsatisfactory responses to or intolerance of other osteoporosis therapies.