Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT

Major alterations in body composition, such as with obesity and weight loss, have complex effects on the measurement of bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA). The effects of altered body fat on quantitative computed tomography (QCT) measurements are unknown. We scanned a spine phantom by DXA and QCT before and after surrounding with sequential fat layers (up to 12 kg). In addition, we measured lumbar spine and proximal femur BMD by DXA and trabecular spine BMD by QCT in 13 adult volunteers before and after a simulated 7.5 kg increase in body fat. With the spine phantom, DXA BMD increased linearly with sequential fat layering at the normal (p < 0.01) and osteopenic (p < 0.01) levels, but QCT BMD did not change significantly. In humans, fat layering significantly reduced DXA spine BMD values (mean ± SD: ?2.2 ± 3.7%, p = 0.05) and increased the variability of measurements. In contrast, fat layering increased QCT spine BMD in humans (mean ± SD: 1.5 ± 2.5%, p = 0.05). Fat layering did not change mean DXA BMD of the femoral neck or total hip in humans significantly, but measurements became less precise. Associations between baseline and fat‐simulation scans were stronger for QCT of the spine (r² = 0.97) than for DXA of the spine (r² = 0.87), total hip (r² = 0.80), or femoral neck (r² = 0.75). Bland‐Altman plots revealed that fat‐associated errors were greater for DXA spine and hip BMD than for QCT trabecular spine BMD. Fat layering introduces error and decreases the reproducibility of DXA spine and hip BMD measurements in human volunteers. Although overlying fat also affects QCT BMD measurements, the error is smaller and more uniform than with DXA BMD. Caution must be used when interpreting BMD changes in humans whose body composition is changing. © 2012 American Society for Bone and Mineral Research     

Change in hip bone mineral density and risk of subsequent fractures in older men

Low bone mineral density (BMD) increases fracture risk; how changes in BMD influence fracture risk in older men is uncertain. BMD was assessed at two to three time points over 4.6 years using dual‐energy X‐ray absorptiometry (DXA) for 4470 men aged ≥65 years in the Osteoporotic Fractures in Men (MrOS) Study. Change in femoral neck BMD was estimated using mixed effects linear regression models. BMD change was categorized as “accelerated” (≤?0.034 g/cm²), “expected” (between 0 and ?0.034 g/cm²), or “maintained” (≥0 g/cm²). Fractures were adjudicated by central medical record review. Multivariate proportional hazards models estimated the risk of hip, nonspine/nonhip, and nonspine fracture over 4.5 years after the final BMD measure, during which time 371 (8.3%) men experienced at least one nonspine fracture, including 78 (1.7%) hip fractures. Men with accelerated femoral neck BMD loss had an increased risk of nonspine (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.4–2.8); nonspine/nonhip (HR = 1.6; 95% CI 1.1–2.3); and hip fracture (HR = 6.3; 95% CI 2.7–14.8) compared with men who maintained BMD over time. No difference in risk was seen for men with expected loss. Adjustment for the initial BMD measure did not alter the results. Adjustment for the final BMD measure attenuated the change in BMD‐nonspine fracture and the change in BMD‐nonspine/nonhip relationships such that they were no longer significant, whereas the change in the BMD‐hip fracture relationship was attenuated (HR = 2.6; 95% CI 1.1–6.4). Total hip BMD change produced similar results. Accelerated decrease in BMD is a strong, independent risk factor for hip and other nonspine fractures in men. © 2012 American Society for Bone and Mineral Research.     

Osteoporosis in COPD outpatients based on bone mineral density and vertebral fractures

One of the extrapulmonary effects of chronic obstructive pulmonary disease (COPD) is osteoporosis. Osteoporosis is characterized by a low bone mineral density (BMD) and microarchitectural deterioration. Most studies in COPD patients use dual‐energy X‐ray absorptiometry (DXA) only to determine osteoporosis; therefore, microarchitectural changes without a low BMD are missed. The aim of this study was to determine the prevalence and correlates of osteoporosis in COPD patients based on DXA, spinal X‐rays, and combinations thereof. DXA and spinal X‐rays were obtained and pulmonary function tests, body composition, 6‐minute walking distance, medical history, and medication use were assessed in 255 clinically stable COPD outpatients of a large teaching hospital in the Netherlands. Half of all patients had radiologic evidence of osteoporosis. Combining the results of DXA with spinal X‐rays augmented the proportion of COPD patients with osteoporosis compared with both methods separately. The prevalence of osteoporosis was not significantly different after stratification for Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) stage. Most patients with osteoporosis did not receive pharmacologic treatment. Age, body mass index (BMI), and parathyroid hormone (PTH) level were significant independent correlates for osteoporosis. Chest physicians should be aware of the high prevalence of osteoporosis in patients with COPD, even in the presence of a low GOLD score, as well as especially in elder COPD patients with a low BMI and/or an increased PTH level. © 2011 American Society for Bone and Mineral Research.     

Effects of bazedoxifene on bone mineral density,bone turnover,and safety in postmenopausal japanese women with osteoporosis

This randomized, double‐blind, placebo‐controlled, dose‐response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (?0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo (p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks (p < .05 for all) and were sustained throughout the study. Total and low‐density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo (p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis. © 2011 American Society for Bone and Mineral Research.     

Differential effects of teriparatide on regional bone formation using 18F‐fluoride positron emission tomography

Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study ¹⁸F‐fluoride plasma clearance (K_i) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1‐hour dynamic scan of the lumbar spine and a 10‐minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K_i values evaluated using a three‐compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K_i values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k₃/[k₂ + k₃]), which increased by 23% (p = .0006). In contrast to K_i, spine SUVs increased by only 3% (p = .84). The discrepancy between changes in K_i and SUVs was explained by a 20% decrease in ¹⁸F^? plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by ¹⁸F^? PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. © 2011 American Society for Bone and Mineral Research.     

Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1-84): a randomized controlled study

Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and high bone mineral density (BMD) despite conventional treatment with calcium supplements and active vitamin D analogues. To assess effects of PTH substitution therapy on 3‐dimensional bone structure, we randomized 62 patients with hypoPT into 24 weeks of treatment with either PTH(1‐84) 100 µg/day subcutaneously or similar placebo as an add‐on therapy. Micro‐computed tomography was performed on 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24 weeks of treatment. Compared with placebo, PTH caused a 27% lower trabecular thickness (p < 0.01) and 4% lower trabecular bone tissue density (p < 0.01), whereas connectivity density was 34% higher (p < 0.05). Trabecular tunneling was evident in 11 (48%) of the biopsies from the PTH group. Patients with tunneling had significantly higher levels of biochemical markers of bone resorption and formation. At cortical bone, number of Haversian canals per area was 139% higher (p = 0.01) in the PTH group, causing a tendency toward an increased cortical porosity (p = 0.09). At different subregions of the hip, areal BMD (aBMD) and volumetric BMD (vBMD), as assessed by dual‐energy X‐ray absorptiometry (DXA) and quantitative computed tomography (QCT), decreased significantly by 1% to 4% in the PTH group. However, at the lumbar spine, aBMD decreased by 1.8% (p < 0.05), whereas vBMD increased by 12.8% (p = 0.02) in the PTH compared with the placebo group. © 2012 American Society for Bone and Mineral Research.     

Habitual flavonoid intakes are positively associated with bone mineral density in women

Dietary flavonoids exert bone-protective effects in animal models, but there is limited information on the effect of different flavonoid subclasses on bone health in humans. The aim of this observational study was to examine the association between habitual intake of flavonoid subclasses with bone mineral density (BMD) in a cohort of female twins. A total of 3160 women from the TwinsUK adult twin registry participated in the study. Habitual intakes of flavonoids and subclasses (flavanones, anthocyanins, flavan-3-ols, polymers, flavonols, and flavones) were calculated from semiquantitative food frequency questionnaires using an updated and extended U.S. Department of Agriculture (USDA) database. Bone density was measured using dual-energy X-ray absorptiometry. In multivariate analyses, total flavonoid intake was positively associated with higher BMD at the spine but not at the hip. For the subclasses, the magnitude of effect was greatest for anthocyanins, with a 0.034 g/cm² (3.4%) and 0.029 g/cm² (3.1%) higher BMD at the spine and hip, respectively, for women in the highest intake quintile compared to those in the lowest. Participants in the top quintile of flavone intake had a higher BMD at both sites; 0.021 g/cm² (spine) and 0.026 g/cm² (hip). At the spine, a greater intake of flavonols and polymers was associated with a higher BMD (0.021 and 0.024 g/cm², respectively), whereas a higher flavanone intake was positively associated with hip BMD (0.008 g/cm²). In conclusion, total flavonoid intake was positively associated with BMD, with effects observed for anthocyanins and flavones at both the hip and spine, supporting a role for flavonoids present in plant-based foods on bone health. © 2012 American Society for Bone and Mineral Research.     

Zoledronic acid improves bone mineral density in pediatric spinal cord injury

Spinal cord injury (SCI) is associated with rapid and sustained bone loss and increase risk of fracture. Disuse is the primary cause for bone loss, although neural and hormonal changes may also contribute via different mechanisms. Bisphosphonates are used widely to treat osteoporosis in adults and are used increasingly for primary and secondary osteoporosis in children. Current data are insufficient to recommend routine use of bisphosphonates for fracture prevention in adult patients post-SCI and there are no available data in pediatric SCI. We report a 12-year-old boy with non-traumatic SCI who was treated with six monthly zoledronic acid (0.05 mg/kg/dose) for 18 months. The patient (AA) was diagnosed with transverse myelitis at 8.1 years of age, resulting in ventilator-dependent incomplete C3 tetraplegia. Following a fragility fracture to the surgical neck of the right humerus at 9.5 years of age, he was started on zoledronic acid. Bone turnover decreased and bone densitometry data (dual-energy X-ray absorptiometry [DXA] and peripheral quantitative computed tomography [pQCT]) showed improvement in metaphyseal and diaphyseal bone mineral content (BMC), volumetric bone mineral density (vBMD), and size, after 18 months of treatment. In the growing skeleton post-SCI, zoledronic acid potentially increases vertebral and long-bone strength by preserving trabecular bone (increased BMC and vBMD) and increasing cortical vBMD and cross-sectional area (CSA).     

Teriparatide increases bone mineral density in a man with osteoporosis pseudoglioma

Osteoporosis Pseudoglioma (OPPG) is characterized by severe juvenile-onset osteoporosis and ocular abnormalities. It is caused by one of several inactivating mutations in LRP5, a gene importantly involved in bone formation. The objective of this study was to evaluate the efficacy of teriparatide in a young man with OPPG. The subject of this case report is a 19-year-old man with congenital blindness and low trauma fractures because of OPPG. A 2-year course of teriparatide, 20 μg/day, was initiated after a 6-year course of intravenous pamidronate infusions, the latter 3 years of which had minimal effects on bone mineral density (BMD). Measurements in serum were made of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (P1NP), total and ionized calcium, phosphate, uric acid, complete blood count, and renal and liver function tests. Urinary calcium/creatinine ratio was determined. BMD was measured by DXA yearly. BMD increased by 9.7% in lumbar spine and 10.2% in right femur hip. CTX rose early, peaking in month 3, followed by an increase in P1NP, peaking in month 9. Both indices returned to baseline by month 24. The increase in CTX followed by P1NP is an unusual time course when teriparatide is used to treat osteoporosis but may be typical of low bone turnover states. There were no adverse events. In a patient with OPPG, teriparatide markedly increased BMD in the lumbar spine and femur hip.     

Selective glucocorticoid receptor modulation maintains bone mineral density in mice

Glucocorticoids (GCs) are potent anti‐inflammatory drugs, but their use is limited by their adverse effects on the skeleton. Compound A (CpdA) is a novel GC receptor modulator with the potential for an improved risk/benefit profile. We tested the effects of CpdA on bone in a mouse model of GC‐induced bone loss. Bone loss was induced in FVB/N mice by implanting slow‐release pellets containing either vehicle, prednisolone (PRED) (3.5 mg), or CpdA (3.5 mg). After 4 weeks, mice were killed to examine the effects on the skeleton using quantitative computed tomography, bone histomorphometry, serum markers of bone turnover, and gene expression analysis. To assess the underlying mechanisms, in vitro studies were performed with human bone marrow stromal cells (BMSCs) and murine osteocyte‐like cells (MLO‐Y4 cells). PRED reduced the total and trabecular bone density in the femur by 9% and 24% and in the spine by 11% and 20%, respectively, whereas CpdA did not influence these parameters. Histomorphometry confirmed these results and further showed that the mineral apposition rate was decreased by PRED whereas the number of osteoclasts was increased. Decreased bone formation was paralleled by a decline in serum procollagen type 1 N‐terminal peptide (P1NP), reduced skeletal expression of osteoblast markers, and increased serum levels of the osteoblast inhibitor dickkopf‐1 (DKK‐1). In addition, serum CTX‐1 and the skeletal receptor activator of NF‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio were increased by PRED. None of these effects were observed with CpdA. Consistent with the in vivo data, CpdA did not increase the RANKL/OPG ratio in MLO‐Y4 cells or the expression of DKK‐1 in bone tissue, BMSCs, and osteocytes. Finally, CpdA also failed to transactivate DKK‐1 expression in bone tissue, BMSCs, and osteocytes. This study underlines the bone‐sparing potential of CpdA and suggests that by preventing increases in the RANKL/OPG ratio or DKK‐1 in osteoblast lineage cells, GC‐induced bone loss may be ameliorated. © 2012 American Society for Bone and Mineral Research.     

Bone biopsy findings and correlation with clinical,radiological, and biochemical parameters in children with fractures

In children the diagnosis of osteoporosis is based on fracture history and DXA‐derived BMD. Bone biopsy is an invasive but accurate method for studying bone characteristics. In this study we evaluated bone biopsy findings and their correlation with noninvasive measures of bone health. Transiliac bone biopsy was performed on 24 consecutive children (17 boys, median age 12 years, range 6 to 16 years) evaluated for suspected primary osteoporosis. Biopsy findings were compared with normative data and correlated with clinical, radiological, biochemical, and densitometric findings. The patients had sustained altogether 64 nonvertebral fractures (median 2.5) from low‐ or moderate‐energy traumas, and 14 patients (58%) had vertebral fractures. The median lumbar spine BMD Z‐score was ?1.2 (range ?3.1 to +1.0). Hypovitaminosis D was present in 58%. Histomorphometry showed low bone volume in 7 patients and normal bone volume in 17. Bone turnover was high in 7, low in 7, and normal in 10 patients. Histomorphometric findings correlated poorly with fracture history, serum bone turnover markers, and DXA findings. Vitamin D deficiency and low lumbar BMD were associated with high bone turnover in the biopsy. These findings underscore the difficulties in diagnosing pediatric osteoporosis. Bone histomorphometry gives additional information and may be useful when considering bisphosphonate treatment in children with suspected primary osteoporosis. © 2011 American Society for Bone and Mineral Research     

Odanacatib in the treatment of postmenopausal women with low bone mineral density: Five years of continued therapy in a phase 2 study

Odanacatib (ODN) is a selective inhibitor of the collagenase cathepsin K that is highly expressed by osteoclasts. In this 2‐year, phase 2, dose‐ranging trial, postmenopausal women with bone mineral density (BMD) T‐scores ?2.0 to ?3.5 at spine or hip were randomized to weekly placebo or ODN 3, 10, 25, or 50 mg plus vitamin D₃ and calcium. Prespecified trial‐extensions continued through 5 years. In year 3, all women were re‐randomized to ODN 50 mg or placebo. For years 4 and 5, women who received placebo or ODN 3 mg in years 1 and 2 and placebo in year 3 received ODN 50 mg; others continued year 3 treatments. Endpoints included lumbar spine (primary), hip, 1/3 radius, and total body BMD; markers of bone metabolism; and safety. Women in the year 4 to 5 extension receiving placebo (n = 41) or ODN 50 mg (n = 100) had similar baseline characteristics. For women who received ODN (10–50 mg) for 5 years, spine and hip BMD increased over time. With ODN 50 mg continually for 5 years (n = 13), mean lumbar spine BMD percent change from baseline (95% confidence interval [CI]) was 11.9% (7.2% to 16.5%) versus ?0.4% (?3.1% to 2.3%) for women who were switched from ODN 50 mg to placebo after 2 years (n = 14). In pooled results of women receiving continuous ODN (10–50 mg, n = 26–29), year 5 geometric mean percent changes from baseline in bone resorption markers cross‐linked N‐telopeptide of type I collagen (NTX)/creatinine and cross‐linked C‐telopeptide (CTX) were approximately ?55%, but near baseline for bone formation markers bone‐specific alkaline phosphatase (BSAP) and amino‐terminal propeptide of type I procollagen (P1NP). In women switched from ODN 10 to 50 mg to placebo after 2 years (n = 25), bone turnover markers were near baseline. In summary, women receiving combinations of ODN (10–50 mg) for 5 years had gains in spine and hip BMD and showed larger reductions in bone resorption than bone formation markers. Discontinuation of ODN resulted in reversal of treatment effects. Treatment with ODN for up to 5 years was generally well‐tolerated. © 2012 American Society for Bone and Mineral Research.     

Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: A three‐year study

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual‐energy X‐ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m²; TBS, 1.178 ± 0.1 but for LS T‐score (ZOL–2.9 ± 1.5 versus PLB–2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus–0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once‐yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years. © 2013 American Society for Bone and Mineral Research.     

Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a −0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (−4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Prevalence of low bone mineral density in a low‐income inner‐city population

Bone mineral density (BMD) is an important factor linked to bone health. Little is known of the prevalence of low BMD and its associated risk factors in an urban underserved population. Between 2001 and 2004, we recruited 338 subjects who completed drug use and medical history questionnaires, underwent hormonal measurements, and underwent whole‐body dual‐energy X‐ray absorptiometry (DXA) for evaluation of BMD and body composition. Of these, 132 subjects had site‐specific DXA (lumbar spine and hip) performed. Osteoporosis was defined as a T‐score of –2.5 or less for men 50 years of age and older and postmenopausal women and a Z‐score of –2.0 or less in men younger than 50 years of age and premenopausal women at either the lumbar spine, total hip, or femoral neck, according to National Osteoporosis Foundation (NOF) guidelines. The cohort consisted of mostly African‐American, middle‐aged people with a high prevalence of illicit drug use, 50% HIV⁺, and 39% hepatitis C⁺. Osteoporosis was identified in 22% of subjects (24 men, 5 women), with the majority of cases (90%) attributable to osteoporosis at the lumbar spine. Osteoporosis was more common in men than in women. Lower whole‐body BMD among women was associated with multiple risk factors, but only with lower lean mass among men. Osteoporosis was highly prevalent in men, mainly at the spine. The risk factors for bone loss in this population need to be further clarified. Screening men for osteoporosis starting at age 50 might be warranted in this population given the multiple risk factors and the unexpectedly high prevalence of low BMD. © 2011 American Society for Bone and Mineral Research.     

Heritability of prevalent vertebral fracture and volumetric bone mineral density and geometry at the lumbar spine in three generations of the Framingham study

Genetic factors likely contribute to the risk for vertebral fractures; however, there are few studies on the genetic contributions to vertebral fracture (VFrx), vertebral volumetric bone mineral density (vBMD), and geometry. Also, the heritability (h²) for VFrx and its genetic correlation with phenotypes contributing to VFrx risk have not been established. This study aims to estimate the h² of vertebral fracture, vBMD, and cross‐sectional area (CSA) derived from quantitative computed tomography (QCT) scans and to estimate the extent to which they share common genetic association in adults of European ancestry from three generations of Framingham Heart Study (FHS) families. Members of the FHS families were assessed for VFrx by lateral radiographs or QCT lateral scout views at 13 vertebral levels (T₄ to L₄) using Genant's semiquantitative (SQ) scale (grades 0 to 3). Vertebral fracture was defined as having at least 25% reduction in height of any vertebra. We also analyzed QCT scans at the L₃ level for integral (In.BMD) and trabecular (Tb.BMD) vBMD and CSA. Heritability estimates were calculated, and bivariate genetic correlation analysis was performed, adjusting for various covariates. For VFrx, we analyzed 4099 individuals (148 VFrx cases) including 2082 women and 2017 men from three generations. Estimates of crude and multivariable‐adjusted h² were 0.43 to 0.69 (p < 1.1 × 10^?2). A total of 3333 individuals including 1737 men and 1596 women from two generations had VFrx status and QCT‐derived vBMD and CSA information. Estimates of crude and multivariable‐adjusted h² for vBMD and CSA ranged from 0.27 to 0.51. In a bivariate analysis, there was a moderate genetic correlation between VFrx and multivariable‐adjusted In.BMD (?0.22) and Tb.BMD (?0.29). Our study suggests vertebral fracture, vertebral vBMD, and CSA in adults of European ancestry are heritable, underscoring the importance of further work to identify the specific variants underlying genetic susceptibility to vertebral fracture, bone density, and geometry. © 2012 American Society for Bone and Mineral Research.     

Mapping Bone Changes at the Proximal Femoral Cortex of Postmenopausal Women in Response to Alendronate and Teriparatide Alone,Combined or Sequentially

Combining antiresorptive and anabolic drugs for osteoporosis may be a useful strategy to prevent hip fractures. Previous studies comparing the effects of alendronate (ALN) and teriparatide (TPTD) alone, combined or sequentially using quantitative computed tomography (QCT) in postmenopausal women have not distinguished cortical bone mineral density (CBMD) from cortical thickness (CTh) effects, nor assessed the distribution and extent of more localized changes. In this study a validated bone mapping technique was used to examine the cortical and endocortical trabecular changes in the proximal femur resulting from an 18‐month course of ALN or TPTD. Using QCT data from a different clinical trial, the global and localized changes seen following a switch to TPTD after an 18‐month ALN treatment or adding TPTD to the ALN treatment were compared. Ct.Th increased (4.8%, p < 0.01) and CBMD decreased (?4.5%, p < 0.01) in the TPTD group compared to no significant change in the ALN group. A large Ct.Th increase could be seen for the switch group (2.8%, p < 0.01) compared to a significantly smaller increase for the add group (1.5%, p < 0.01). CBMD decreased significantly for the switch group (–3.9%, p < 0.01) and was significantly different from no significant change in the add group. Ct.Th increases were shown to be significantly greater for the switch group compared to the add group at the load bearing regions. This study provides new insights into the effects of ALN and TPTD combination therapies on the cortex of the proximal femur and supports the hypothesis of an increased bone remodeling by TPTD being mitigated by ALN. © 2014 American Society for Bone and Mineral Research.     

Central (ICV) leptin injection increases bone formation,bone mineral density,muscle mass,serum IGF‐1, and the expression of osteogenic genes in leptin‐deficient ob/ob mice

Both central and peripheral leptin administrations reduce body weight, food intake, and adiposity in ob/ob mice. In this study we compared effects of intracerebroventricular (ICV) and subcutaneous (SC) administration of leptin on bone metabolism in the appendicular and axial skeleton and adipose tissue gene expression and determined the effects of ICV leptin on bone marrow gene expression in ob/ob mice. In experiment 1, leptin (1.5 or 0.38 µg/d) or control was continuously injected ICV for 12 days. Gene expression analysis of femoral bone marrow stromal cells showed that expression of genes associated with osteogenesis was increased after ICV injection, whereas those associated with osteoclastogenesis, adipogenesis, and adipocyte lipid storage were decreased. In experiment 2, leptin was injected continuously ICV (0.0 or 1.5 µg/d) or SC (0.0 or 10 µg/d) for 12 days. In both experiments, regardless of mode of administration, leptin decreased body weight, food intake, and body fat and increased muscle mass, bone mineral density, bone mineral content, bone area, marrow adipocyte number, and mineral apposition rate. Serum insulin was decreased, whereas serum osteocalcin, insulin‐like growth factor 1, osteoprotegerin, pyridinoline, and receptor activator of nuclear factor κB ligand concentrations were increased. In experiment 2, expression of genes in adipose tissue associated with apoptosis, lipid mobilization, insulin sensitivity, and thermogenesis was increased, whereas expression of genes associated with cell differentiation and maturation was decreased regardless of mode of administration. Thus ICV injection of leptin promotes expression of pro‐osteogenic factors in bone marrow, leading to enhanced bone formation in ob/ob mice. © 2011 American Society for Bone and Mineral Research     

Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass

Romosozumab, a monoclonal antibody that binds sclerostin, has a dual effect on bone by increasing bone formation and reducing bone resorption, and thus has favorable effects in both aspects of bone volume regulation. In a phase 2 study, romosozumab increased areal BMD at the lumbar spine and total hip as measured by DXA compared with placebo, alendronate, and teriparatide in postmenopausal women with low bone mass. In additional analyses from this international, randomized study, we now describe the effect of romosozumab on lumbar spine and hip volumetric BMD (vBMD) and BMC at month 12 as assessed by QCT in the subset of participants receiving placebo, s.c. teriparatide (20 µg once daily), and s.c. romosozumab (210 mg once monthly). QCT measurements were performed at the lumbar spine (mean of L₁ and L₂ entire vertebral bodies, excluding posterior processes) and hip. One year of treatment with romosozumab significantly increased integral vBMD and BMC at the lumbar spine and total hip from baseline, and compared with placebo and teriparatide (all p < 0.05). Trabecular vertebral vBMD improved significantly and similarly from baseline (p < 0.05) with both romosozumab (18.3%) and teriparatide (20.1%), whereas cortical vertebral vBMD gains were larger with romosozumab compared with teriparatide (13.7% versus 5.7%, p < 0.0001). Trabecular hip vBMD gains were significantly larger with romosozumab than with teriparatide (10.8% versus 4.2%, p = 0.01), but were similar for cortical vBMD (1.1% versus –0.9%, p = 0.12). Cortical BMC gains were larger with romosozumab compared with teriparatide at both the spine (23.3% versus 10.9%, p < 0.0001) and hip (3.4% versus 0.0%, p = 0.03). These improvements are expected to result in strength gains and support the continued clinical investigation of romosozumab as a potential therapy to rapidly reduce fracture risk in ongoing phase 3 studies. © 2016 American Society for Bone and Mineral Research.