Baseline Bone Mineral Density Research Articles

How to predict fragility fracture beyond 10 years? The OFELY study.

Low bone mineral density (BMD) is a major determinant of fragility fractures (Fx), but its very long-term prediction is poorly documented. We analyzed the risk of Fx beyond 10 years in women. In a longitudinal cohort study (Os des Femmes de Lyon), we studied 867 women aged 40 years and older (mean age 59 ± 10 y) over 20 years. We assessed the risk of the first incident Fx according to the baseline BMD obtained by dual-energy X-ray absorptiometry, clinical risk factors, and the Fracture Risk Assessment Tool (FRAX). During a median (interquartile range) follow-up of 20 years (3), 245 women sustained one or more incident fragility Fx. Women who sustained a first Fx beyond 10 years (Fx 10-20, n = 109) were younger and had lower values of FRAX compared with those in the first 10 years (Fx 0-10, n = 136). After adjustment for age, they still had greater grip strength and BMD. Parental hip Fx was associated with an increased risk of Fx 10-20 but contrasting with Fx 0-10, the risk of Fx 10-20 was not associated with age, previous Fx, and FRAX except in women younger than 70 years. Each SD decrease of BMD at the spine, femoral neck, total hip, and ultradistal radius was associated with an increased risk of Fx 10-20 with adjusted odds ratios [95% confidence interval (CI)] of 1.43 (95% CI 1.12-1.82), 1.39 (95% CI 1.08-1.82), 1.47 (95% CI 1.14-1.89), and 2.00 (95% CI 1.47-2.7). Women with osteoporosis had an increased risk of both Fx 0-10 and Fx 10-20 compared with women with normal BMD, whereas osteopenia was not associated with a higher risk of Fx beyond 10 years. Low BMD in women is significantly associated with an increased risk of Fx over 20 years. Beyond 10 years, the prediction conferred by baseline BMD was better than that from clinical risk factors.

Zoledronic acid prevents decreases in bone mineral density in patients with prostate cancer undergoing combined androgen blockade.

The aim of this study was to evaluate the effect of zoledronic acid (ZA) on bone mineral density (BMD) in patients with prostate cancer receiving combined androgen blockade (CAB) as a first-line androgen deprivation therapy. Patients receiving CAB for prostate cancer without bone metastasis were candidates for this study. Forty-two patients were randomly assigned to receive either ZA or no treatment. BMD were measured at baseline and at 12 months. Bone-turnover markers, including cross-linked N-telopeptide of type I collagen (NTX), C-telopeptide of type I collagen (ICTP), and bone-specific alkaline phosphatase (BAP), were assessed during study periods. Patients on ZA maintained BMD after a year of treatment. Change in T-score from baseline differed significantly between the two groups (P=0.009). An inverse correlation was demonstrated between baseline and change in T-score in the ZA group. While ZA prevented an increase in ICTP and BAP, the increase in NTX was suppressed only in patients with low baseline T-score. ZA prevented a decrease in BMD in patients undergoing CAB, especially those with lower baseline BMD.

A model of BMD changes after alendronate discontinuation to guide postalendronate BMD monitoring.

Women stopping alendronate are commonly monitored with serial bone mineral density (BMD) measurements, yet no information exists on how frequently or for whom these measurements should be performed. The objective of the study was to develop a tool to guide post-alendronate BMD monitoring. A predictive model was constructed to estimate the time until a given percentage of women's BMD T-scores drop below a given threshold that indicates a management change (such as retreatment) would be considered. This model was then used to estimate the time it would take for groups of women defined by their baseline BMDs to drop below the given threshold. Data were derived from the Fracture Intervention Trial Long Term Extension (FLEX), the largest multicenter clinical trial of its type to date. Four hundred four women who had received an average of 5.1 years of alendronate during the Fracture Intervention Trial and were subsequently observed for 5 treatment-free years (on placebo) during the FLEX trial were used to estimate the change in BMD over time. If a management change such as alendronate reinitiation would be considered when BMD T-score drops below -2.5, the model shows that women with total hip BMD greater than -1.9 T-scores at the time of alendronate discontinuation have less than a 20% probability that at follow-up, monitoring BMD will be below the threshold within 5 years. The model performed similarly, and results are provided over a range of management change thresholds from -1.75 to -3 T-scores. Using the tool developed in this analysis, it is possible to estimate when BMD repeat measurement after alendronate discontinuation could potentially be useful. Measuring BMD within 5 years after alendronate discontinuation is unlikely to change management for women with total hip BMD 0.6 T-scores above a prespecified retreatment threshold within the range of -1.75 to -3 T-scores.

A survey of steroid-related osteoporosis diagnosis, prevention and treatment practices of pediatric rheumatologists in North America.

BackgroundThe purpose of our study is to assess practices of North American pediatric rheumatologists regarding monitoring, prevention, and treatment of low bone mineral density (BMD) in children on long-term glucocorticoid treatment.Long-term glucocorticoid therapy is associated with accelerated bone loss. Children with JIA and lupus have low baseline BMD and incident vertebral fractures commonly occur in these groups of patients even after a relatively short period of time being on systemic glucocorticoids. There are no established guidelines for identification, prevention, and treatment of glucocorticoid-induced bone loss in children.MethodsA cross-sectional online survey was conducted with 199 physicians who were listed in the ACR database as practicing pediatric rheumatology in North America.Results86 physicians (43%) responded; 87% were board-certified in pediatric rheumatology. 95% used dual energy X-ray absorptiometry as their primary modality for assessing BMD. 79% “rarely” or “never” obtained a baseline BMD measurement prior to initiation of glucocorticoid therapy. 42% of respondents followed BMD annually. 93% “frequently” or “always” prescribed calcium for patients on long-term corticosteroid therapy; 81% “frequently” or “always” prescribed vitamin D. In patients diagnosed with osteoporosis, 35%-50 % of the practitioners “sometimes”, “frequently” or “always” prescribed bisphosphonates. Bisphosphonates are prescribed at similar rates for male and female patients, and slightly more frequently for pubertal than for pre-pubertal patients. 96% of respondents “rarely” or “never” prescribed calcitonin for patients on long-term glucocorticoid therapy; 92% “rarely” or “never” prescribe this medication for patients with known osteopenia or osteoporosis.ConclusionsUtilization of DXA in children on long-term corticosteroid therapy varies greatly among North American pediatric rheumatologists. Most respondents do not screen for low BMD on a regular basis despite acknowledging the risks of bone loss in this population. Broad consensus appears to be present among practitioners favoring the prescription of calcium and vitamin D for patients receiving long-term corticosteroid therapy. Relatively few respondents consistently recommend bisphosphonate therapy, even for patients with known low bone density; calcitonin is rarely used. These data underscore the need for studies to acquire specific data on bone loss, and its prevention and treatment in young patients on long-term glucocorticoid therapy.

Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with growth hormone deficiency (GHD): the Leiden Cohort Study.

Growth hormone deficiency (GHD) in adulthood may be associated with a decreased bone mineral density (BMD), a decreased bone mineral content (BMC) and an increased fracture risk. Recombinant human GH (rhGH) replacement induces a progressive increase in BMD for up to 5-7years of treatment. Data on longer follow-up are, however, scarce. Two hundred and thirty-adult GHD patients (mean age 47·1years, 52·6% female), of whom 88% patients had adult-onset (AO) GHD, receiving rhGH replacement for ≥5years were included in the study. Most patients had multiple pituitary hormone deficiencies. Bone turnover markers, BMC and BMD and T-scores at the lumbar spine and femoral neck were evaluated at baseline, and after 5, 10 and 15years of rhGH replacement. In addition, clinical fracture incidence was assessed. Mean lumbar spine BMD, lumbar spine BMC and T-scores gradually increased during the first 10years of rhGH replacement and remained stable thereafter. Largest effects of rhGH supplementation were found in men. In the small subset of patients using bisphosphonates, use of bisphosphonates did not impact additional beneficial effects in the long term. Low baseline BMD positively affected the change in BMD and BMC over time, but there was a negative effect of high GH dose at 1year on the change in BMD and BMC over time. Clinical fracture incidence during long-term rhGH replacement was 20.1/1000py. Fifteen years of rhGH replacement in GHD adults resulted in a sustained increase in BMD values at the lumbar spine, particularly in men, and stabilization of BMD values at the femoral neck. Clinical fracture incidence was suggested not to be increased during long-term rhGH replacement.

PTH-115 Prevalence Rates And Risk Factors For Osteoporosis In Patients With Coeliac Disease

IntroductionThe optimal timing for performing a baseline bone mineral density (BMD) in Coeliac disease (CD) patients is controversial. European guidelines published in 1998 recommended a baseline BMD at diagnosis. One...

AB0248 Analysis of Bone Mineral Density at the Hand by Radiogrammetry and Dual X-RAY Absorptiometry as A Predictor of Severity in Early Rheumatoid Arthritis Patients. Comparative Study

BackgroundThe evaluation of cortical bone mineral density (BMD) on metacarpal bones by digital radiogrammetry (DXR) has been proven to be a simple, reliable and predictive method to evaluate the severity...

AB0808 Incomplete Distal Renal Tubular Acidosis in Patients with Osteo-Porosis/Osteopenia – Prevalence and Treatment

BackgroundImpaired renal H+ ion secretion causes acid retention which is known to promote bone dissolutionObjectivesTo prospectively assess the prevalence of distal renal tubular acidosis (dRTA) in low bone mass patients...

OP0260 Denosumab for Patients Receiving Long-Term Glucocorticoids Who do not Have Adequate Response to Bisphosphonate Treatment: A Randomized Controlled Trial

ObjectivesTo evaluate the efficacy of denosumab on bone mineral density (BMD) in patients receiving long-term glucocorticoids who do not have satisfactory response to bisphosphonate treatment.MethodsPatients who were receiving long-term prednisolone...

Hyperkyphosis, Kyphosis Progression, and Risk of Non-Spine Fractures in Older Community Dwelling Women: The Study of Osteoporotic Fractures (SOF)

While accentuated kyphosis is associated with osteoporosis, it is unknown whether it increases risk of future fractures, independent of bone mineral density (BMD) and vertebral fractures. We examined the associations of baseline Cobb angle kyphosis and 15 year change in kyphosis with incident non-spine fractures using data from the Study of Osteoporotic Fractures. A total of 994 predominantly white women, aged 65 or older, were randomly sampled from 9704 original participants to have repeated Cobb angle measurements of kyphosis measured from lateral spine radiographs at baseline and an average of 15 years later. Non-spine fractures, confirmed by radiographic report, were assessed every 4 months for up to 21.3 years. Compared with women in the lower three quartiles of kyphosis, women with kyphosis greater than 53° (top quartile) had a 50% increased risk of non-spine fracture (95% CI, 1.10-2.06 after adjusting for BMD, prevalent vertebral fractures, prior history of fractures, and other fracture risk factors. Cobb angle kyphosis progressed an average of 7° (SD = 6.8) over 15 years. Per 1 SD increase in kyphosis change, there was a multivariable adjusted 28% increased risk of fracture (95% CI, 1.06-1.55) that was attenuated by further adjustment for baseline BMD (HR per SD increase in kyphosis change, 1.19; 95% CI 0.99-1.44). Greater kyphosis is associated with an elevated non-spine fracture risk independent of traditional fracture risk factors in older women. Furthermore, worsening kyphosis is also associated with increased fracture risk that is partially mediated by low baseline BMD that itself is a risk factor for kyphosis progression. These results suggest that randomized controlled fracture intervention trials should consider implementing kyphosis measures to the following: (1) further study kyphosis and kyphosis change as an additional fracture risk factor; and (2) test whether therapies may improve or delay its progression.

Bone Health Care for Patients With Prostate Cancer Receiving Androgen Deprivation Therapy

Patients with prostate cancer often receive androgen deprivation therapy (ADT) as part of their treatment regimen. However, treatment with ADT causes multiple side effects, including reduced bone mineral density (BMD), lower lean body mass, and a higher risk for fractures. Several organizations provide clinical practice guidelines for osteoporosis screening, prevention, and treatment in this population, but adherence to these guidelines remains low. Areas for improvement in provider adherence include baseline and follow-up BMD testing, as well as counseling regarding healthy bone behaviors such as calcium/vitamin D intake, lifestyle changes, and physical exercise. Comparison of osteoporosis care in breast cancer and non-oncology populations shows that suboptimal bone health care is not isolated to prostate cancer. A summary of the literature examining improvements in patient adherence and provider delivery of bone health care is included in this review, but high-quality studies are lacking. Patients may be the most receptive to written educational information delivered at or near the time of ADT initiation. Involvement of a primary care practitioner and oncologist in care delivery is associated with higher BMD test use. Institution-level programs that automatically initiate osteoporosis screening and management may be effective at reducing the incidence of hip fracture. Lastly, suggestions are provided for future approaches to knowledge translation and quality of care studies to improve bone health.

Mediolateral subchondral tibial bone mineral density difference does not predict osteoarthritis progression.

Data on the relationship between osteoporosis and osteoarthritis are conflicting. Most studies report "snapshot" prevalences, and there are few studies evaluating localized knee bone mineral density (BMD) measurements with respect to subsequent osteoarthritis progression. The authors hypothesize that increased mediolateral difference of the proximal tibial BMD may predict progression of knee osteoarthritis. In this study, 246 female volunteers were followed up prospectively over 2 years. Baseline BMD measurements of bilateral proximal (subchondral) tibiae were performed, and the mediolateral BMD ratio was calculated. Precision studies were performed on healthy volunteers to validate the technique. The patients were divided into osteoarthritis progressors and non-progressors based on Kellgren-Lawrence radiographic criteria at 2-year follow-up. Patients who were taking bisphosphonates or who had a history of inflammatory, infectious, or metabolic bone disease and previous hip and knee surgery were excluded. Demographic data, calcium supplementation, physical activity, baseline knee radiographs, and radiographs at 2-year follow-up were obtained. The study was adequately powered to detect an effect size of 0.4. There were 121 progressors and 125 non-progressors. Mean mediolateral BMD ratio was 1.02 among the progressors and 1.01 among the non-progressors (t=0.632, P=.528). Potential confounders were equally distributed among both groups. The data suggest that there is no link between proximal tibial BMD ratio and progression of knee osteoarthritis.

Magnesium intake, bone mineral density, and fractures: results from the Women’s Health Initiative Observational Study

Magnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear. We examined magnesium intake as a risk factor for osteoporotic fractures and altered bone mineral density (BMD). This prospective cohort study included 73,684 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Total daily magnesium intake was estimated from baseline food-frequency questionnaires plus supplements. Hip fractures were confirmed by a medical record review; other fractures were identified by self-report. A baseline BMD analysis was performed in 4778 participants. Baseline hip BMD was 3% higher (P < 0.001), and whole-body BMD was 2% higher (P < 0.001), in women who consumed >422.5 compared with <206.5 mg Mg/d. However, the incidence and RR of hip and total fractures did not differ across quintiles of magnesium. In contrast, risk of lower-arm or wrist fractures increased with higher magnesium intake [multivariate-adjusted HRs of 1.15 (95% CI: 1.01, 1.32) and 1.23 (95% CI: 1.07, 1.42) for quintiles 4 and 5, respectively, compared with quintile 1; P-trend = 0.002]. In addition, women with the highest magnesium intakes were more physically active and at increased risk of falls [HR for quintile 4: 1.11 (95% CI: 1.06, 1.16); HR for quintile 5: 1.15 (95% CI: 1.10, 1.20); P-trend < 0.001]. Lower magnesium intake is associated with lower BMD of the hip and whole body, but this result does not translate into increased risk of fractures. A magnesium consumption slightly greater than the Recommended Dietary Allowance is associated with increased lower-arm and wrist fractures that are possibly related to more physical activity and falls.

Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate

Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study. A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate). In two previous multicenter, open-label studies, postmenopausal women ≥55years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60mg subcutaneously every 6months (N = 852) or oral BP 150mg monthly (N = 851) for 12months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed. In the overall population, denosumab was associated with greater gains in BMD at 12months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8%), femoral neck (1.8 vs 0.3%), and lumbar spine (3.7 vs 1.4%) (p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups. Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.

Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana.

BackgroundTenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis (PrEP) has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD) loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women.MethodWe evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18–29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA) scans at the hip, spine, and forearm.ResultsA total of 220 participants (108 TDF-FTC, 112 placebo) had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8%) participants had low baseline BMD (z-score of <−2.0 at any anatomic site), including 3/114 women (2.6%) and 12/106 men (11.3%) (p = 0.02). Low baseline BMD was associated with being underweight (p = 0.02), having high blood urea nitrogen (p = 0.02) or high alkaline phosphatase (p = 0.03), and low creatinine clearance (p = 0.04). BMD losses of >3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0%) TDF-FTC vs. 26/79 (32.9%) placebo; p = 0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm −0.84% (p = 0.01), spine −1.62% (p = 0.0002), hip −1.51% (p = 0.003)].ConclusionUse of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons.Trial RegistrationClinicalTrials.gov NCT00448669

Hip Fractures and Bone Mineral Density in the Elderly—Importance of Serum 25-Hydroxyvitamin D

BackgroundThe significance of serum 25-hydroxyvitamin D [25(OH)D] concentrations for hip fracture risk of the elderly is still uncertain. Difficulties reaching both frail and healthy elderly people in randomized controlled trials or large cohort studies may in part explain discordant findings. We determined hazard ratios for hip fractures of elderly men and women related to serum 25(OH)D, including both the frail and the healthy segment of the elderly population.MethodsThe AGES-Reykjavik Study is a prospective study of 5764 men and women, age 66–96 years, based on a representative sample of the population of Reykjavik, Iceland. Participation was 71.8%. Hazard ratios of incident hip fractures and baseline bone mineral density were determined according to serum concentrations of 25(OH)D at baseline.ResultsMean follow-up was 5.4 years. Compared with referent values (50–75 nmol/L), hazard ratios for hip fractures were 2.24 (95% CI 1.63, 3.09) for serum 25(OH)D <30 nmol/L, adjusting for age, sex, body mass index, height, smoking, alcohol intake and season, and 2.08 (95% CI 1.51, 2.87), adjusting additionally for physical activity. No difference in risk was associated with 30–50 nmol/L or ≥75 nmol/L in either model compared with referent. Analyzing the sexes separately, hazard ratios were 2.61 (95% CI 1.47, 4.64) in men and 1.93 (95% CI 1.31, 2.84) in women. Values <30 nmol/L were associated with significantly lower bone mineral density of femoral neck compared with referent, z-scores -0.14 (95% CI −0.27, −0.00) in men and −0.11 (95% CI −0.22, −0.01) in women.ConclusionsOur results lend support to the overarching importance of maintaining serum 25(OH)D above 30 nmol/L for bone health of elderly people while potential benefits of having much higher levels could not be detected.

Bone Loss around a Stable, Partly Threaded Hydroxyapatite-Coated Cup: A Prospective Cohort Study Using Rsa and Dxa

Aseptic loosening of the acetabular component is the most common reason for revision after primary THA, and periprosthetic demineralisation has been described as a potential cause for this process. The trabeculae-oriented pattern (TOP)-cup is a flat, hydroxyapatite (HA)-coated titanium shell with a threaded rim that was developed in order to minimise periprosthetic bone loss. We hypothesised that this cup provides good primary stability and improves preservation of periprosthetic bone mineral density (BMD). A prospective cohort study on 30 patients receiving the TOP cup was carried out. Preoperative total hip BMD and postoperative periprosthetic BMD in five periprosthetic regions of interest were investigated by dual energy radiographic absorptiometry (DXA), cup migration was analysed by radiostereometry (RSA), and the Harris hips score (HHS) was determined. Mean HHS increased from 49 (24-79) preoperatively to 99 (92-100) after two years. DXA after one year demonstrated substantial BMD loss in the proximal periprosthetic zones 1 (-18%), zone 2 (-16 %) and zone 3 (-9%, all p<0.001 when compared with baseline BMD determined immediately postoperatively). The bone loss in these regions did not recover after two years. RSA (performed on 16 patients) showed that only very limited micromotion of the implant occurred: Mean cranial migration was 0.01 mm (95% confidence interval (CI): -0.09-0.12) and mean inclination decreased by 0.02º (CI: -0.43-0.39) after two years. We conclude that the TOP cup provides good primary stability in the short-term. However, substantial BMD loss in proximal periprosthetic areas indicates that the design of this cup cannot prevent periprosthetic bone loss that has also been observed around other uncemented cups.

Association of farnesyl diphosphate synthase polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis

Background Genetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China. Methods The study group comprised 639 postmenopausal women aged (62.2±7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (β-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment. Results The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6±84.1) mg/cm2) than those with AC genotypes ((703.0±86.9) mg/cm2) and AA genotypes ((649.8±62.4) mg/cm2) (P &lt;0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P &lt;0.05). Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype. Conclusions FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.

Romosozumab in Postmenopausal Women with Low Bone Mineral Density

BackgroundSclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation.MethodsIn a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of −2.0 or less at the lumbar spine, total hip, or femoral neck and −3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator — oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover.ResultsAll dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups.ConclusionsIn postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.)

Changes in Bone Mineral Density After Sleeve Gastrectomy or Gastric Bypass: Relationships with Variations in Vitamin D, Ghrelin, and Adiponectin Levels

A major long-term concern after gastric bypass (GBP) is the risk of osteoporosis; however, little is known about this complication in patients undergoing sleeve gastrectomy (SG). To evaluate changes in bone mineral density (BMD) after GBP and SG, and its relationship with changes in vitamin D, parathyroid hormone (PTH), ghrelin, and adiponectin. Twenty-three women undergoing GBP (BMI 42.0 ± 4.2 kg/m2; 37.3 ± 8.1 years) and 20 undergoing SG (BMI 37.3 ± 3.2 kg/m2; 34.2 ± 10.2 years) were studied before and 6 and 12 months after surgery. BMD was measured by dual-energy X-ray absorptiometry. Plasma PTH, 25-hydroxyvitamin D (25-OHD), ghrelin, and adiponectin concentrations were determined. Food as well as calcium and vitamin D supplement intake was recorded. Excess weight loss (mean ± SE), adjusted by baseline excess weight, was 79.1±3.8% and 74.9 ± 4.1% 1 year after GBP and SG, respectively (p = 0.481). Significant reduction in BMD for total body (TB), lumbar spine (LS), and femoral neck (FN) was observed after GBP. In the SG group, reduction in BMD was significant only for TB. Adjusted by baseline BMD, the difference between change in BMD for GBP vs. SG was not significant for TB, LS, or FN. Percent reduction in ghrelin concentration was a main factor related to total BMD loss (GBP group) and LS BMD loss (GBP and SG groups). One year after gastric bypass, bone mineral density was significantly affected, mainly at the femoral neck. Decreases in bone mineral density were more dramatic among patients who had greater baseline BMD and greater reduction in ghrelin concentrations.