Examining the link between bariatric surgery, bone loss, and osteoporosis: a review of bone density studies

As the popularity of bariatric surgery to treat morbid obesity has risen, so has a concern of increased skeletal fragility secondary to accelerated bone loss following bariatric procedures. We reviewed cross-sectional and prospective literature reporting bone density outcomes following bariatric surgical treatment for morbid obesity. Prospective research provides evidence of hip and lumbar spine areal bone mineral density (aBMD) reductions primarily in women despite calcium and vitamin D supplementation. Femoral neck aBMD declines of 9–11% and lumbar spine aBMD reductions up to 8% were observed at the first post-operative year following malabsorptive procedures. Mean T- and Z-scores up to 25 years following surgery remained within normal and healthy ranges. Of those studies reporting development of osteoporosis following gastric bypass, one woman became osteoporotic after 1 year. Despite observed bone loss in the hip region post-surgery, data do not conclusively support increased incidence of osteoporosis or increased fracture risk in post-bariatric patients. However, given the limitations of dual energy X-ray absorptiometry technology in this population and the relative lack of long-term prospective studies that include control populations, further research is needed to provide conclusive evidence regarding fracture outcomes in this population.     

Relationship Between Bariatric Surgery and Bone Mineral Density: a Meta-analysis

Background

A meta-analysis regarding bone loss after bariatric surgery, designed to compare surgical and nonsurgical groups, has not yet been performed. Therefore, we performed a meta-analysis to compare the differences between bariatric surgical groups and nonoperated controls with regard to bone mineral density.

Methods

In March 2015, we performed a review of the literature using PubMed, EMBASE, and the Cochrane Library. The search focused on retrospective and prospective studies, including but not limited to randomized studies published in English.

Results

Among 1299 studies that were initially screened, ten met the selection criteria. For all types of bariatric surgery, bone density at the femoral neck was lower in the surgical group than in the nonsurgical control group (mean difference [MD] ?0.05 g/cm²; 95 % confidence interval [CI], ?0.07 to ?0.02; p?=?0.001); no difference in bone density was found between the two groups at the lumbar spine (MD ?0.01 g/cm²; 95 % CI ?0.07 to 0.05; p?=?0.661). The analysis of Roux-en-Y gastric bypass showed similar results.

Conclusion

Bone density at the femoral neck decreased after bariatric surgery, compared to that in nonsurgical controls, whereas bone density at the lumbar spine did not show a difference between groups. Further larger scale studies with comparative nonsurgical controls are warranted to overcome the heterogeneity among studies in this analysis and to add evidence of possible bone loss subsequent to bariatric surgical procedures.

     

Ultrasound parameters and markers of bone turnover in hyperthyroidism: a longitudinal study.

Hyperthyroid patients are characterized by accelerated bone turnover leading to bone mass loss. The aim of this study was to assess changes in quantitative ultrasound [QUS] parameters, bone mineral density (BMD), and biochemical markers of bone turnover in patients prior to and after the onset of hyperthyroid treatment. A 2-yr longitudinal study was performed on 10 women recently diagnosed with Grave's disease after starting antithyroid therapy. Six patients were postmenopausal. All patients showed evidence of thyrotoxicosis as indicated by suppressed serum TSH and high levels of total serum thyroxine. They received antithyroid therapy (methimazole and/or 131I radiodine). QUS parameters were measured using an Achilles ultrasound unit and BMD was assessed by dual-energy X-ray absorptiometry (DXA). Thyroid hormones and markers of bone turnover were determined at baseline and 6, 12, and 24 mo after the onset of treatment.Stiffness, broadband ultrasound attenuation (BUA), and speed of sound (SOS) were low at baseline compared to normal values for the same age range and increased after 2 yr of treatment. A significant increase in BMD of the lumbar spine, total skeleton, and skeletal regions (legs) was also observed after treatment. Recovery of stiffness was almost complete at 12 mo. No significant elevation was observed between 12 and 24 mo. Stiffness increased 7.6%, 10.4%, and 10.4% after 6 mo (p < 0.02), after 1 yr (p < 0.02), and after 2 yr, respectively. No significant increase in SOS and BUA was observed between 12 and 24 mo. Furthermore, recovery of total skeleton and lumbar spine BMD continued throughout the study. Successful antithyroid therapy produced a rapid increase in QUS parameters (Stiffness) and spine BMD and femoral neck during the first year of treatment and a slower increment in total skeleton (up to 24 mo). Overall, ad integrum restitution was not observed in QUS or BMD.     

Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study

A decrease in bone mineral density (BMD) is a major complication of renal transplantation (RTx), predominantly occurring within the first 6 mo after RTx. The most important causative factor is the use of corticosteroids, but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too. This study examines the effect of treatment with calcium and active vitamin D on the loss of BMD in the first 6 mo after RTx. A total of 111 renal transplant recipients (65 men, 46 women; age, 47 +/- 13 yr) were randomized to either treatment with active vitamin D (0.25 microg/d) plus calcium (1000 mg/d) (CaD group), or to no treatment (NoT group). Immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate mofetil. Laboratory parameters and BMD (lumbar spine and hip) were measured at 0, 1 (laboratory only), 3, and 6 mo after RTx. Lumbar BMD was nearly normal at the time of RTx. In both groups, a significant decrease in lumbar BMD was observed during the first 3 mo (CaD, -3.3 +/- 4.3%; P < 0.0001; NoT, -4.1 +/- 4.8%; P < 0.0001). Between the third day and sixth month, lumbar BMD slightly recovered in the CaD group, but it decreased further in the NoT group (total loss 0 to 6 mo: CaD, -2.6 +/- 5.0% [P < 0.001]; NoT, -5.0 +/- 4.7% [P < 0.0001]). As a result, the amount of bone loss at 6 mo was significantly lower in the CaD group (P = 0.02). Loss of BMD at the different femoral sites was also significantly reduced in the CaD group. Apart from a trend toward more frequent hypercalcemia in the CaD group, no clinical or biochemical differences existed between the groups. Treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 mo after RTx.     

Longitudinal changes in bone density in hyperparathyroidism.

Primary hyperparathyroidism (HPTH) is a known risk factor for cortical bone loss. The primary objective of this study was to examine the time course and location of changes in bone mass within the first year after parathyroidectomy (PAX). The secondary goal was to evaluate the efficacy of combined estrogen therapy and parathyroidectomy in postmenopausal women. Thirty-two subjects with primary HPTH participated in a prospective, longitudinal study for at least 1 yr. Twenty-seven subjects underwent PTX, while five received no therapy (control). Among the PTX patients, 21 were postmenopausal women, and 8 of these women also received estrogen. Subjects had serial measurements of parathyroid hormone levels, serum chemistries, and bone density at multiple sites. Among all PTX patients, lumbar spine, hip, and whole body bone mineral content increased significantly (3.8-6%; p < 0.005) at 12 mo, with most of the increments observed by 3 mo. In postmenopausal women, estrogen treatment resulted in higher increments in the femoral neck (8.6 +/- 2% vs 4.9 +/- 1.2%, respectively; p = 0.07) and the whole body (6 +/- 2% vs 2.4 +/- 1.6%, respectively; p = 0.07). In HPTH, early and generalized increments in bone mass follow PTX, and the combination of surgery with estrogen therapy may be superior to surgery without estrogen treatment. A randomized, controlled trial including PTX, estrogen, and a combination of the two is needed to determine the optimal therapy in postmenopausal women.     

Bone mineral density and broadband ultrasound attenuation with estrogen treatment of postmenopausal women.

The purpose of the current study was to determine the changes in lumbar spine, hip, and calcaneus bone mineral density (BMD), and in calcaneus broadband ultrasound attenuation (BUA) in early menopausal women and to assess the effects of estrogen replacement therapy (ERT) on bone mass at these sites over a 2-yr period. Fifty-three Caucasian women who were at least 6 mo postmenopausal were divided into two groups based on estrogen use. Twenty-one women, average age 53.0 +/- 0.6 yr and 2.9 +/- 0.3 yr since menopause, had been receiving estrogen in combination with progesterone for at least 6 mo prior to enrollment in the study. Thirty-two women, average age 52.7 +/- 0.8 yr and 2.8 +/- 0.3 yr since menopause, had never received ERT. During the 2-yr study, women not receiving ERT had significant decreases in BMD of the spine -2.3 +/- 0.6%, femoral neck -2.2 +/- 0.8%, and calcaneus -4.7 +/- 0.9%, and in BUA of the calcaneus -14.3 +/- 1.8%. ERT prevented the decreases in BMD at the spine +0.4 +/- 0.6% and calcaneus -2.3 +/- 1.1%, but did not prevent a significant decrease in bone mass at the femoral neck -1.9 +/- 0.8% and BUA at the calcaneus -17.8 +/- 3.2%. Neither group had significant decreases in total hip BMD. This study demonstrates again that ERT prevents the menopause-associated decreases in spine BMD. However, in this group of women, ERT did not prevent loss in femoral neck BMD or BUA. The results suggest that women being treated with estrogen for maintenance of BMD in early menopause need to be monitored to ensure efficacy of therapy, especially in the maintenance of femoral neck BMD.     

Clinical utility of spine bone density in elderly women.

It is common clinical practice to obtain a bone density measurement at both the hip and spine to evaluate osteoporosis. With aging, degenerative changes in the lumbar spine may elevate the bone mineral density (BMD) results giving false assurances that the fracture risk at the spine is low. We examined the association of spine osteoarthritis and bone mineral density in 1082 community-dwelling ambulatory older women aged 50-96 years who participated in a 1992-1996 osteoporosis research clinic visit. The BMD was measured at the hip and posteroanterior (PA) and lateral lumbar spine using dual energy X-ray absorptiometry (DXA). Spine osteoarthritis was identified on the PA lumbar spine DXA images by a musculoskeletal radiologist. Forty percent of women had evidence of spine osteoarthritis (OA). Women with spine OA had a mean age of 77.4 yr (95% confidence interval [CI]: 76.5-78.2), were significantly older than women without spine OA (mean age, 66.8 yr; 95% CI: 65.9-67.7), and were more likely to have prevalent radiographic fractures (14.2% vs. 9.5%; p<0.05). Age-adjusted BMD at the femoral neck, total hip, PA spine, and lateral spine was significantly higher in women with spine OA. Women with spine OA were more likely to have osteoporosis by the World Health Organization classification at the femoral neck and total hip than those without spine OA, but less likely based on the PA spine (14.4% vs. 24.5%). Despite higher BMD levels, women with OA of the lumbar spine had higher prevalence of osteoporosis at the hip and more radiographic vertebral fractures. In elderly women 65 yr and older who are likely to have spine OA, the DXA measurement of the spine may not be useful in assessing fracture risk, and DXA of the hip is recommended for identification of osteoporosis.     

Preventing bone loss in renal transplant recipients with vitamin D

Very rapid bone loss, osteopenia, and osteoporosis have been documented in the first 6 to 12 mo after renal transplantation. Investigated was the effect of treatment with active vitamin D on the prevention of posttransplantation bone loss. Forty adult men who were recent renal transplant recipients were enrolled onto the study. Patients were randomized into two groups: group 1 received daily alfacalcidol 0.5 micro g by mouth, and group 2 (control) received placebo. Every patient in both groups received daily 500-mg calcium carbonate supplements. Parameters of bone metabolism and bone mineral density measured at three sites were assessed before and after the study period. Bone mineral density was increased by 2.1%, 1.8%, and 3.2% at lumbar spine, femoral neck, and forearm, respectively, in group 1, whereas it decreased by 3.2%, 3.8%, and 1.8% at the same sites in the control group (P < 0.05). Serum intact parathyroid hormone level decreased significantly in group 1 compared with the control group (P = 0.003). Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol. Use of alfacalcidol early after transplantation is safe and well tolerated.     

Utility of Spine Bone Mineral Density in Fracture Prediction Within FRAX

Predicting individuals at risk for fracturing and modifying that risk are important in preventative health. Our aim was to quantify the impact of spine bone mineral density (BMD) on fracture risk prediction and determine the positive predictive value of fracture prediction using the lowest BMD value at the femoral neck, total hip, or lumbar spine. A retrospective cross-sectional analysis of 15,033 women was performed, assessing the contribution of age, body mass index, number of clinical risk factors, T-score, and osteoporosis category to the presence of fracture. In patients whose lumbar spine T-scores are 1 or 2 osteoporosis categories lower than femoral neck, there is an approximately 30% increased risk of fracture compared with the femoral neck alone. For patients younger than 60 yr, the odds ratio of having a fracture based on the presence of lumbar spine osteoporosis was greater than that based on femoral neck osteoporosis. Osteoporosis at the total hip correlated best with the presence of fracture. When using FRAX, we recommend that the 10-yr fracture prediction be adjusted when lumbar spine T-score is 1–2 osteoporosis categories lower than the femoral neck T-score or when lumbar spine T-score is ≥1 standard deviation less than femoral neck T-score.     

Monitoring alendronate and estradiol therapy with quantitative ultrasound and bone mineral density.

Few studies have compared quantitative ultrasound with bone mineral density (BMD) in monitoring response to therapy in osteoporosis. The aim of our study was to compare finger ultrasound variables and BMD for monitoring alendronate and estradiol therapy in postmenopausal women. We recruited 26 women aged 50 to 79 yr (mean: 65 yr) with osteoporosis; 18 patients received 10 mg/d of alendronate and 500 mg/d of calcium carbonate and 8 patients received 500 mg/d of calcium carbonate only. We recruited 21 hysterectomized postmenopausal women who were randomized to treatment or control. The treatment group received a 25-mg estradiol implant, which was replaced every 6 mo. The control group had a sham procedure. In the alendronate group, there were significant changes at 1 yr at the lumbar spine (p<0.05), bone transmission time (p<0.01), and pure speed of sound (p<0.001) and the changes continued into the second year. In the estradiol implant group, there were significant changes at 1 yr at the lumbar spine (p<0.001), the femoral neck (p<0.05), and the pure speed of sound (p<0.01). For alendronate, the signal-to-noise ratio was similar between the lumbar spine and bone transmission time (1.8 and 1.4) and greater than for the pure speed of sound and femoral neck (0.8 and 0.7); for estradiol, the signal-to-noise ratio was similar between the lumbar spine and femoral neck (2.0 and 1.5) and greater than for the pure speed of sound and bone transmission time (1.1 and 0.6).These results indicated that changes in finger ultrasound are similar in clinical utility to dual-energy X-ray absorptiometry measurements at the femoral neck for the monitoring of antiresorptive treatments for osteoporosis.     

Effects of Bazedoxifene on BMD and Bone Turnover in Postmenopausal Women: 2‐Yr Results of a Randomized,Double‐Blind,Placebo‐, and Active‐Controlled Study

Osteoporosis is an increasingly common health concern in postmenopausal women. In a 2‐yr phase III study, bazedoxifene prevented bone loss, reduced bone turnover, and was well tolerated in early postmenopausal women with normal or low BMD. Introduction : Bazedoxifene is a novel selective estrogen receptor modulator that has increased BMD and bone strength in experimental models, without stimulating breast or uterus. This 24‐mo, randomized, double‐blind study assessed the efficacy and safety of three doses of bazedoxifene compared with placebo and raloxifene in the prevention of postmenopausal osteoporosis. Materials and Methods : Healthy postmenopausal women with a BMD T‐score at the lumbar spine or femoral neck between –1.0 and ?2.5 or clinical risk factors for osteoporosis were randomly assigned to one of five groups: bazedoxifene 10, 20, or 40 mg/d, placebo, or raloxifene 60 mg/d. All women received elemental calcium. Efficacy outcomes included changes from baseline through 24 mo in BMD of the lumbar spine, hip, femoral neck, and femoral trochanter and biomarkers of bone metabolism. Results : The intent‐to‐treat population included 1434 women (mean age, 58 yr; mean time from last menstrual period, 11 yr). All doses of bazedoxifene and raloxifene prevented bone loss, whereas in the placebo group, there was significant loss of BMD at all skeletal sites. Mean differences in percent change in lumbar spine BMD from baseline to 24 mo relative to placebo were 1.08 ± 0.28%, 1.41 ± 0.28%, 1.49 ± 0.28%, and 1.49 ± 0.28% for 10, 20, and 40 mg bazedoxifene and 60 mg raloxifene, respectively (p < 0.001 for all comparisons). Comparable BMD responses were observed at other body sites. Significant and comparable decreases in serum osteocalcin and C‐telopeptide levels from baseline and relative to placebo with active treatment were observed as early as 3 mo and were sustained through study conclusion (p < 0.001). Overall incidences of adverse events, serious adverse events, and discontinuations caused by adverse events were similar between groups. The most common adverse events included headache, infection, arthralgia, pain, hot flush, and back pain. Conclusions : Treatment with bazedoxifene prevented bone loss and reduced bone turnover equally as well as raloxifene and was generally well tolerated in postmenopausal women with normal/low BMD.     

Short- and Mid-term Changes in Bone Mineral Density After Laparoscopic Sleeve Gastrectomy

Background

Bariatric surgery is the most effective treatment for achieving a significant weight loss. Morbidities present a significant reduction after bariatric surgery, but it may also result in several health complications, related to nutritional deficiencies, including bone metabolism. Several studies have reported a decrease in bone mineral density (BMD), but most of them referring to malabsorptive procedures. Restrictive procedures do not imply changes in gastrointestinal anatomy, so that one may expect fewer metabolic disturbances.

Methods

We performed a retrospective observational study of all morbidly obese patients undergoing LSG between 2008 and 2011 at our institution. Bone densitometry was performed before surgery and 1 and 2 years after the intervention. Body size measurements, analytical variables and densitometric values in the lumbar spine (BMD, t score and z score) were investigated.

Results

Forty-two patients were included, 39females and 3males. Mean BMI was 51.21 kg/m². Mean excessive BMI loss was 79.9 % after 1 year and 80.6 % after 2 years. Mean BMD values for spine increased progressively, reaching statistical significance at 1 and at 2 years. Percentage of BMD increase was 5.7 % at 1 year and 7.9 % at 2 years. An inverse correlation was observed between BMD increase and parathyroid hormone (PTH) decrease and a direct correlation between BMD and vitamin D increase.

Conclusion

Bone mineral density showed a progressive increase during the first and second year after sleeve gastrectomy. BMD changes are not associated with weight loss, but showed a direct correlation with vitamin D and an inverse correlation with PTH levels.     

Regional bone loss after orthotopic liver transplantation in inbred rats: the role of hepatic denervation

Bone loss and long-term persistence of osteoporosis with increased fracture risk are common after liver transplantation. It is unknown whether transplantation-induced disruption of hepatic nerves, serving numerous regulatory metabolic and sensory functions, is herein involved. To test this possibility, we measured bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and studied dynamic histomorphometry, radiocalcium kinetics, and biochemical parameters in 7 liver-transplanted and 7 sham-operated inbred rats. Although liver function was normal in TX rats, trabecular BMD of the first lumbar vertebra and total BMD of the femoral diaphysis were decreased by 13% and 6%, respectively, 9 months postsurgery. The breaking force of the femur was significantly lower by 21%. However, bone mass in the femoral and tibial metaphysis was preserved as evidenced by pQCT measurements and histomorphometry. Trabecular width and wall thickness were significantly decreased in vertebral cancellous bone, whereas indices of bone formation and resorption were normal or slightly reduced. Serum minerals, mineral balance, fractional and net absorption of Ca and Mg, serum calciotropic hormones, IGF-I, leptin, specific activity of 45Ca in bone, 45Ca excretion, and biochemical indices of bone formation and bone resorption remained unchanged. We conclude that liver transplantation-related denervation causes cancellous and cortical bone loss in well-innervated bone sites such as the lumbar spine and the long bone diaphysis. Cancellous bone loss in TX rats is due to an impairment of osteoblast team performance and subsequent trabecular thinning. The mechanism uncovered by our study may contribute to long-term bone loss after liver transplantation.     

Choice of Lumbar Spine Bone Density Reference Database for Fracture Prediction in Men and Women: A Population-Based Analysis

The diagnosis of osteoporosis in men is controversial, although most studies demonstrate similar fracture rates for men and women with the same level of hip bone mineral density (BMD). Whether this applies to the lumbar spine is currently uncertain and has important implications with respect to choice of reference population for T-score calculation and osteoporosis diagnosis. This question was specifically addressed in the population-based Canadian Multicentre Osteoporosis Study cohort of 4745 women and 1887 men ages 50+ yr at the time of baseline lumbar spine dual energy x-ray absorptiometry. In up to 10 yr of observation, incident clinical major osteoporotic fractures occurred in 110 men (5.8%) vs 543 women (11.4%) (p < 0.001). Mean lumbar spine BMD in men was greater than in women, both among those with and those without incident major osteoporotic fracture (p < 0.001). Men were at slightly lower risk for incident major osteoporotic fracture than women for an equivalent lumbar spine BMD (age- and BMD-adjusted rate ratio 0.75, 95% confidence interval 0.60–0.93, p = 0.008) with similar findings after adjustment for the World Health Organization fracture risk assessment clinical risk factors or competing mortality. No significant sex difference in the BMD relationship was seen for vertebral fractures (clinical or radiographic) or for all fractures. In summary, this large population-based longitudinal cohort study found similar or lower fracture risk for men vs women after adjustment for absolute lumbar spine BMD and additional covariates. The least complicated model for describing fracture risk is therefore to use the same reference lumbar spine data for generating T-scores in men and women.     

Bone Health in Children and Adolescents After Renal Transplantation

The basis for lifelong bone health is established in childhood and adolescence. Whereas pediatric renal transplant (RTx) patients are at risk for impaired bone mass gain and fractures, scarce data on this subject are available. We performed a cross‐sectional and longitudinal study of bone health in a national cohort of 106 pediatric RTx patients (median age, 12.6 yr; median follow‐up, 5.1 yr after RTx). The patients underwent clinical evaluation, DXA for BMD, and spinal imaging for vertebral fractures. In longitudinal analysis, the median lumbar spine BMD Z‐score was lowest (median, ?1.0) at 1 yr postoperatively but increased to a peak value of ?0.2 at 5 yr. In boys, the lumbar spine BMD Z‐score increased also during puberty but decreased in girls. In cross‐sectional analysis, the lumbar spine, hip, and whole body BMD Z‐scores were < ?2 SD in 4%, 6%, and 6% of the patients, respectively. Sixteen percent had sustained peripheral fractures, and 8% had vertebral fractures. Female sex and age >15 yr (OR, 56.26; 95% CI, 5.17–611.82; p = 0.0007) as well as high plasma PTH levels (OR, 4.03; 95% CI, 1.37–11.85; p = 0.009) were significant predictors for low BMD. Three‐year cumulative glucocorticoid dose, outside the immediate post‐RTx years, was not associated with BMD parameters. The observed BMD results were satisfactory. However, the high (8%) prevalence of vertebral fractures warrants careful evaluation of bone health in these patients.     

Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD.

Denosumab is a monoclonal antibody to RANKL. In this randomized, placebo-controlled study of 412 postmenopausal women with low BMD, subcutaneous denosumab given every 3 or 6 mo was well tolerated, increased BMD, and decreased bone resorption markers for up to 24 mo. Continued study of denosumab is warranted in the treatment of low BMD in postmenopausal women. INTRODUCTION: Denosumab is a fully human monoclonal antibody that inhibits RANKL, a key mediator of osteoclastogenesis and bone remodeling. This prespecified exploratory analysis evaluated the efficacy and safety of denosumab through 24 mo in the treatment of postmenopausal women with low BMD. MATERIALS AND METHODS: Four hundred twelve postmenopausal women with lumbar spine BMD T-scores of -1.8 to -4.0 or femoral neck/total hip T-scores of -1.8 to -3.5 were randomly assigned to receive double-blind, subcutaneous injections of placebo; denosumab 6, 14, or 30 mg every 3 mo; denosumab 14, 60, 100, or 210 mg every 6 mo; or open-label oral alendronate 70 mg once weekly. Outcome measures included BMD at the lumbar spine, total hip, distal one-third radius, and total body; bone turnover markers; and safety. RESULTS: Denosumab increased BMD at all measured skeletal sites and decreased concentrations of bone turnover markers compared with placebo at 24 mo. At the lumbar spine, BMD increases with denosumab ranged from 4.13% to 8.89%. BMD changes with denosumab 30 mg every 3 mo and > or =60 mg every 6 mo were similar to, or in some cases greater than, with alendronate. The incidence of adverse events was similar in the placebo, denosumab, and alendronate treatment groups. Exposure-adjusted adverse events over 2 yr of treatment were similar to those reported during the first year of treatment. CONCLUSIONS: In these postmenopausal women with low BMD, treatment with denosumab for 2 yr was associated with sustained increases in BMD and reductions in bone resorption markers compared with placebo.     

Genetic effects on bone loss in peri- and postmenopausal women: a longitudinal twin study.

This longitudinal twin study was designed to assess the heritability of bone loss in peri- and postmenopausal women. A sample of 724 female twins was studied. Baseline and repeat BMD measurements were performed. Results of genetic model-fitting analysis indicated genetic effects on bone loss account for approximately 40% of the between-individual variation in bone loss at the lumbar spine, forearm, and whole body. INTRODUCTION: BMD and bone loss are important predictors of fracture risk. Although the heritability of peak BMD is well documented, it is not clear whether bone loss is also under genetic regulation. This study was designed to assess the heritability of bone loss in peri- and postmenopausal women. MATERIALS AND METHODS: A sample of 724 female twins (177 monozygotic [MZ] and 185 dizygotic [DZ] pairs), 45-82 yr of age, was studied. Each individual had baseline BMD measurements at the lumbar spine, hip, forearm, and total body by DXA and at least one repeat measure, on average 4.9 yr later. Change in BMD (DeltaBMD) was expressed as percent of gain or loss per year. Intraclass correlation coefficients for DeltaBMD were calculated for MZ and DZ pairs. Genetic model-fitting analysis was conducted to partition the total variance of DeltaBMD into three components: genetic (G), common environment (C), and specific environment, including measurement error (E). The index of heritability was estimated as the ratio of genetic variance over total variance. RESULTS: The mean annual DeltaBMD was -0.37 +/- 1.43% (SD) per year at the lumbar spine, -0.27 +/- 1.32% at the total hip, -0.77 +/- 1.66% at the total forearm, -0.36 +/- 1.56% at the femoral neck, and -0.16 +/- 0.81% at the whole body. Intraclass correlation coefficients were significantly higher in MZ than in DZ twins for all studied parameters, except at the hip sites. Results of genetic model-fitting analysis indicated that the indices of heritability for DeltaBMD were 0.38, 0.49, and 0.44 for the lumbar spine, total forearm, and whole body, respectively. However, the genetic effect on DeltaBMD at all hip sites was not significant. CONCLUSIONS: These data suggest that, although genetic effects on bone loss with aging are less pronounced than on peak bone mass, they still account for approximately 40% of the between-individual variation in bone loss for the lumbar spine, total forearm, and whole body in peri- and postmenopausal women. These findings are relevant for studies aimed at identification of genes that are involved in the regulation of bone loss.     

Prevalence of vertebral compression fracture deformity by X-ray absorptiometry of lateral thoracic and lumbar spines in a population referred for bone densitometry.

The presence of a vertebral compression fracture has been demonstrated to be a predictor of future fracture independent of bone mineral density in prospective cohort studies. Fan-beam densitometers are now available that can image the thoracic and lumbar spines and detect deformities consistent with fracture. We report a pilot study of 342 patients referred for bone densitometry who had lateral vertebral imaging performed. Fifty patients (14.6%) of the entire cohort had one or more vertebral deformities identified on lateral vertebral imaging. Seventy-three patients (21.3%) of the entire cohort were 60 or more years of age and had osteopenia by World Health Organization (WHO) criteria (T-score: -1.0 to -2.4 at the spine, total hip, or femoral neck). Twenty of these patients (27.4%) had one or more vertebral deformities. Without identifying prevalent vertebral deformities, these individuals at high risk for fracture may not be offered pharmacologic therapy to reduce fracture risk. Therefore, it may be reasonable to obtain lateral vertebral imaging at least for individuals age > or =60 yr who have mild to moderate bone loss at the spine or hip.     

Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy

PURPOSE: We characterize the consequences of androgen deprivation therapy on body composition in elderly men. MATERIALS AND METHODS: Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months. RESULTS: At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001). CONCLUSIONS: Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.     

Clinical Factors Associated With Trabecular Bone Score

Dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) is the reference standard for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel grey-level texture measurement that can be extracted from DXA images, predicts osteoporotic fractures independent of BMD. Our aim was to identify clinical factors that are associated with baseline lumbar spine TBS. In total, 29,407 women ≥50 yr at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Multiple linear regression and logistic regression (lowest vs highest tertile) was used to define the sensitivity of TBS to other risk factors associated with osteoporosis. Only a small component of the TBS measurement (7–11%) could be explained from BMD measurements. In multiple linear regression and logistic regression models, reduced lumbar spine TBS was associated with recent glucocorticoid use, prior major fracture, rheumatoid arthritis, chronic obstructive pulmonary disease, high alcohol intake, and higher body mass index. In contrast, recent osteoporosis therapy was associated with a significantly lower likelihood for reduced TBS. Similar findings were seen after adjustment for lumbar spine or femoral neck BMD. In conclusion, lumbar spine TBS is strongly associated with many of the risk factors that are predictive of osteoporotic fractures. Further work is needed to determine whether lumbar spine TBS can replace some of the clinical risk factors currently used in fracture risk assessment.