Denosumab Densitometric Changes Assessed by Quantitative Computed Tomography at the Spine and Hip in Postmenopausal Women With Osteoporosis

FREEDOM was a phase 3 trial in 7808 women aged 60–90 yr with postmenopausal osteoporosis. Subjects received placebo or 60 mg denosumab subcutaneously every 6 mo for 3 yr in addition to daily calcium and vitamin D. Denosumab significantly decreased bone turnover; increased dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD); and significantly reduced new vertebral, nonvertebral, and hip fractures. In a subset of women (N = 209), lumbar spine, total hip, and femoral neck volumetric BMD (vBMD) were assessed by quantitative computed tomography at baseline and months 12, 24, and 36. Significant improvement from placebo and baseline was observed in aBMD and vBMD in the denosumab-treated subjects at all sites and time points measured. The vBMD difference from placebo reached 21.8%, 7.8%, and 5.9%, respectively, for the lumbar spine, total hip, and femoral neck at 36 mo (all p ≤ 0.0001). Compared with placebo and baseline, significant increases were also observed in bone mineral content (BMC) at the total hip (p < 0.0001) largely related to significant BMC improvement in the cortical compartment (p < 0.0001). These results supplement the data from DXA on the positive effect of denosumab on BMD in both the cortical and trabecular compartments.     

Improvements in hip trabecular,subcortical, and cortical density and mass in postmenopausal women with osteoporosis treated with denosumab

In the FREEDOM study, denosumab treatment (60 mg every 6 months) decreased bone resorption, increased bone mineral density (BMD), and reduced new vertebral, nonvertebral, and hip fractures over 36 months in postmenopausal women with osteoporosis. In a subset of these women, hip quantitative computed tomography (QCT) was performed at baseline and months 12, 24, and 36. These scans were analyzed using Medical Image Analysis Framework (MIAF) software, which allowed assessment of total hip integral, trabecular, subcortical, and cortical compartments; the cortical compartment was further divided into 2 areas of interest (outer and inner cortex). This substudy reports changes in BMD and bone mineral content (BMC) from baseline and compared placebo with denosumab over 36 months of treatment (placebo N = 26; denosumab N = 36). Denosumab treatment resulted in significant improvements in total hip integral volumetric BMD (vBMD) and BMC from baseline at each time point. At month 36, the mean percentage increase from baseline in total hip integral vBMD and BMC was 6.4% and 4.8%, respectively (both p < 0.0001). These gains were accounted for by significant increases in vBMD and BMC in the trabecular, subcortical, and cortical compartments. In the placebo group, total hip integral vBMD and BMC decreased at month 36 from baseline by − 1.5% and − 2.6%, respectively (both p < 0.05). The differences between denosumab and placebo were also significant at months 12, 24, and 36 for integral, trabecular, subcortical, and cortical vBMD and BMC (all p < 0.05 to < 0.0001). While the largest percentage differences occurred in trabecular vBMD and BMC, the largest absolute differences occurred in cortical vBMD and BMC. In summary, denosumab significantly improved both vBMD and BMC from baseline and placebo, assessed by QCT MIAF, in the integral, trabecular, subcortical, and cortical hip compartments, all of which are relevant to bone strength.     

Comparison of proximal femur and vertebral body strength improvements in the FREEDOM trial using an alternative finite element methodology

Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.6%) strength in sideways fall configuration at 36 months, estimated in Newtons by an established voxel-based finite element (FE) methodology. Since FE analyses rely on the choice of meshes, material properties, and boundary conditions, the aim of this study was to independently confirm and compare the effects of denosumab on vertebral and femoral strength during the FREEDOM trial using an alternative smooth FE methodology. Unlike the previous FE study, effects on femoral strength in physiological stance configuration were also examined. QCT data for the proximal femur and two lumbar vertebrae were analyzed by smooth FE methodology at baseline, 12, 24, and 36 months for 51 treated (denosumab) and 47 control (placebo) subjects. QCT images were segmented and converted into smooth FE models to compute bone strength. L1 and L2 vertebral bodies were virtually loaded in axial compression and the proximal femora in both fall and stance configurations. Denosumab increased vertebral body strength by 10.8%, 14.0%, and 17.4% from baseline at 12, 24, and 36 months, respectively (p < 0.0001). Denosumab also increased femoral strength in the fall configuration by 4.3%, 5.1%, and 7.2% from baseline at 12, 24, and 36 months, respectively (p < 0.0001). Similar improvements were observed in the stance configuration with increases of 4.2%, 5.2%, and 5.2% from baseline (p ≤ 0.0007). Differences between the increasing strengths with denosumab and the decreasing strengths with placebo were significant starting at 12 months (vertebral and femoral fall) or 24 months (femoral stance). Using an alternative smooth FE methodology, we confirmed the significant improvements in vertebral body and proximal femur strength previously observed with denosumab. Estimated increases in strength with denosumab and decreases with placebo were highly consistent between both FE techniques.     

Eating disorders,menstrual dysfunction,weight change and DMPA use predict bone density change in college-aged women

IntroductionThere are limited longitudinal studies that have evaluated bone mineral density (BMD) changes in college-aged women. Our objective was to simultaneously evaluate factors influencing 4-year BMD change.MethodsThis was a longitudinal cohort study of healthy, physically active women in the US Military Academy (n = 91; average age = 18.4 years). Assessments over four years included: height, weight, calcium intake, physical fitness, menstrual function (annual number cycles), oral contraceptives (OCs) or depot-medroxyprogesterone acetate (DMPA) use, and eating disorder behavior (Eating Disorder Inventory; (EDI)). BMD was measured annually at the lumbar spine and total hip by dual X-ray absorptiometry and calcaneal BMD by PIXI. Slope of 4 year BMD change at each skeletal site (spine total hip and calcaneus) was calculated for each woman.ResultsBMD gains occurred at the spine in 50% and the hip in 36% of women. In unadjusted analyses, spine bone gain was positively related to menstrual cycle frequency (p = 0.04). Spine and hip BMD loss occurred in those using DMPA (p < 0.01) and those with the highest EDI quartile scores (p < 0.05). BMD change was unrelated to OC use. Hip and calcaneus BMD decreased with weight loss (average 4.8 + 2.2 lb/year) as compared to those with stable weight/weight gain (p < 0.05). In multivariable analysis, spine BMD increase was significantly related to African American (AA) race, normal EDI score and normal menses. Hip BMD increase was related to AA race, weight increase and normal menses. DMPA use was associated with spine, hip, and calcaneus bone loss.ConclusionOn average, BMD may modestly increase in college-aged women, in the absence of risk factors. However, risk factors including subclinical eating disorders, weight loss, menstrual dysfunction and DMPA use can have significant detrimental effects on BMD in young healthy physically active women.     

Effect of immobilization,off-loading and zoledronic acid on bone mineral density in patients with acute Charcot neuroarthropathy: A prospective randomized trial

BackroundBisphosphonates are commonly used as an adjuvant in the management of acute Charcot neuroarthropathy (CNA), although the clinical efficacy of the treatment is controversial. The aim of the present study is to investigate the effect of immobilization and zoledronic acid on bone mineral density (BMD) changes during the treatment of acute CNA.MethodsThirty-five patients with acute midfoot CNA were randomly assigned to treatment with either zolendronic acid or placebo. BMD of the lumbar spine and both hips was measured at baseline and after six months of treatment.ResultsComparison between BMD at presentation and at 6 months demonstrated a significant fall in BMD in the placebo group at the CNA-affected femoral neck (?3.2%, p = 0.016) and in the CNA-free hip (?1.2%, p = 0.026). Conversely, a significant rise in BMD was observed in the zolendronic acid group at all measured areas of the CNA-free hip.Discussion and conclusionsImmobilization and off-loading does not lead to marked disuse osteoporosis in patients with acute CNA after 6 months of treatment. Treatment with zoledronic acid led to a statistically significant increase in hip BMD compared to placebo.     

Bone mineral density changes following discontinuation of ronacaleret treatment: Off-treatment extension of a randomized,dose-finding phase II trial

ContextParathyroidectomy in patients with hyperparathyroidism can produce subsequent increases in bone mineral density (BMD). Ronacaleret, a selective calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release, induced mild hyperparathyroidism.ObjectiveThe aim of this study is to evaluate whether BMD changes after cessation of ronacaleret treatment.DesignObservational, off-treatment, extension of a randomized, placebo-controlled, dose-ranging phase II trial.SettingFifteen academic centers in seven countries.PatientsPostmenopausal women with low BMD; 171 out of 569 women in the parent study were enrolled in the extension study.InterventionsSubjects were treated with ronacaleret 100 mg (n = 16), 200 mg (n = 38), 300 mg (n = 35), or 400 mg (n = 32) once daily, alendronate 70 mg (n = 17) once weekly, or matching placebo (n = 33) for 10–12 months; BMD was measured after discontinuation of ronacaleret or alendronate treatment.Main outcome measureMean percent change in lumbar spine areal BMD by dual-energy X-ray absorptiometry at 6–12 months after discontinuing ronacaleret or alendronate compared with the 10- to 12-month BMD measurement of the parent study.ResultsAt the lumbar spine, all doses of ronacaleret resulted in gains in BMD while on treatment. These increases in BMD were maintained or increased after discontinuation of ronacaleret. All doses of ronacaleret caused bone loss at the total hip while on active treatment. However, there was an attenuation of this loss in the off-treatment extension study.ConclusionThe gain in BMD at the lumbar spine was maintained post-treatment and the loss of BMD at the total hip was attenuated. We hypothesize that there may have been some bone remineralization after cessation of ronacaleret.     

Changes in bone mineral density after allogenic stem cell transplantation

ObjectiveOsteoporosis is a complication after allogenic stem cell transplantation (alloSCT). The purpose of this study was to assess changes in bone mineral density (BMD) 6 months and 3 years after alloSCT, as well as predictors of bone loss.MethodsA longitudinal, prospective, single-center study was conducted at Lille University Hospital between 2005 and 2016. Clinical, biological, radiologic (thoracic and lumbar spine) and densitometric (DXA) assessments were carried out at baseline (pre-transplant), 6 months and 3 years. Patients with myeloma were not included.ResultsTwo hundred and fifty-eight patients were included (144 men). Among them, 60.1% had leukemia and 65.8% of them, acute myeloid leukemia. At baseline, 6 months and 3 years, DXA-confirmed that osteoporosis was observed in 17%, 22.8% and 17.5% of the patients, respectively, mainly at the femoral neck. At baseline, 6 months and 3 years, 9 (8.5%), 53 (21.5%) and 38 (16.7%) patients, respectively, were receiving anti-osteoporotic treatment. From baseline to 6-month follow-up, BMD decreased significantly (p < 0.001) at the lumbar spine (?36 [95%CI; ?51 to ?20] mg/cm² of hydroxyapatite), femoral neck (?43 [95%CI; ?57 to ?29] mg/cm² of hydroxyapatite) and total hip (?53 [95%CI; ?68 to ?39] mg/cm² of hydroxyapatite). From 6-month to 3-year follow-up, a significant increase in BMD was observed at the lumbar spine only (+31 [95%CI; 20 to 42] mg/cm² of hydroxyapatite, p < 0.001). At all 3 sites, changes in BMD did not differ between patients treated or untreated by anti-osteoporotic treatment from 6-month to 3 year follow-up. Incident fractures were found in 4.1% and 5.7% of the patients at 6 months and 3 years, respectively. Between baseline and 6 months, bone loss at all 3 sites was associated with corticosteroid intake. At the total hip, 23.3% of the decrease in BMD from baseline to 6 months was due to an active hematological disease (p < 0.05), a bone marrow stem cells (p < 0.01) and a corticosteroid intake (p < 0.01).ConclusionOur study found evidence of bone fragility in alloSCT patients. Low BMD persisted at the hip 3 years after transplantation due to slower improvement at this site.     

Efficacy and safety of 2 g/day of strontium ranelate in Asian women with postmenopausal osteoporosis

Strontium ranelate is a new effective anti-osteoporotic treatment having a unique mode of action, reducing bone resorption while promoting continued bone formation, with a broad range of anti-fracture efficacy at vertebral as well as peripheral sites. In Phase III studies, it has proven its early and sustained efficacy against vertebral fractures in Caucasians along with a significant increase in lumbar bone mineral density (BMD). The aim of this randomized double-blind study was to demonstrate the efficacy of strontium ranelate (2 g/day) on lumbar spine bone mineral density and the clinical and biological safety in Asian postmenopausal osteoporotic patients compared to placebo over 1 year. Three hundred and twenty-nine eligible women from mainland China, Hong Kong and Malaysia were randomized into the study. The baseline characteristics were similar in the treatment and placebo groups: mean age of 66.2 ± 6.5 years, time since menopause 17.6 ± 7.2 years. In the Full Analysis Set (FAS, N = 302), the mean baseline lumbar L2–L4 BMD was 0.715±0.106 g/cm² in the strontium ranelate group and 0.708 ± 0.109 g/cm² in the placebo group. The mean baseline femoral neck BMD was 0.575 ± 0.074 g/cm² and 0.566 ± 0.069 g/cm² respectively and mean total hip BMD was 0.642 ± 0.080 g/cm² and 0.631 ±0.088 g/cm² respectively. The overall compliance was 91.4% in the study drug group, and 97.4% in the placebo group. After 1 year of treatment, the lumbar spine, femoral neck and total hip BMD in the treated group was significantly increased by 3–5% as compared to placebo. Strontium ranelate was well tolerated. The most frequently reported emergent adverse events were comparable in both groups (60.4% versus 60.0%), with majority of them being mild gastrointestinal disorders. There were no clinically relevant changes in laboratory tests, such as blood routine, hepatic and renal function. It is thus concluded that the effects of 2 g/day strontium ranelate on BMD and its safety profile in this cohort of postmenopausal osteoporotic Asian women were consistent with results obtained from Caucasian women in which the efficacy on the reduction in risk of fracture has been proven.     

Baseline MRI inflammation is not a determinant of 5-year bone mineral density loss in patients with early spondyloarthritis

ObjectiveThe aim of this study was to assess the effect of baseline inflammation on Magnetic Resonance Imaging (MRI) on the change in Bone Mineral Density (BMD) over 5 years in patients with early spondyloarthritis (SpA).MethodsFrom the patients of the DESIR cohort (an early axial SpA cohort), patients with BMD data at both baseline and 5 years, and baseline spine and sacroiliac joints MRI were included. Inflammation was assessed with the SpondyloArthritis Research Consortium of Canada (SPARCC) spine score. Significant BMD loss was defined by a change of > 0.03 g/cm². No patients had received TNF blockers before inclusion in the cohort. Univariate and multivariable prognostic analyses were performed. An inverse propensity score weighting method was used to handle confounders.ResultsOne hundred and eighty-three patients were included (mean age 33.9 ± 8.7 years, 58.5% men). A significant bone loss was reported in 51% (n = 92) of patients at either lumbar spine or hip. Fourteen (7%) patients had low BMD (Z-score < −2) at the end of the follow-up vs. 28 (15%) at baseline. In multivariable analysis, age was a protective factor of 5 year-BMD loss at any site (OR = 0.96, 95% CI [0.93–0.99]). Baseline MRI inflammation has no significant effect on BMD change at any site (OR= 0.84, 95% CI [0.46–1.53]).ConclusionHalf of patients with early SpA have a significant bone loss at either lumbar spine or hip over 5 years. Baseline MRI inflammation is not a determinant of this bone loss.     

Effects of combined whole-body vibration and resistance training on muscular strength and bone metabolism in postmenopausal women

Whole-body vibration (WBV) has been shown to be osteogenic in animal models; however, its application in humans is not clear. The purpose of this study was to examine the effects of an 8-month program involving WBV plus resistance training on bone mineral density (BMD) and bone metabolism in older postmenopausal women. Fifty-five estrogen-deficient postmenopausal women were assigned to a resistance training group (R, n = 22), a WBV plus resistance training group (WBVR, n = 21), or a control group (CON, n = 12). R and WBVR performed upper and lower body resistance exercises 3 days/week at 80% 1 Repetition Maximum (1RM). WBVR received vibration (30–40 Hz, 2–2.8g) in three different positions preceding the resistance exercises. Daily calcium intake, bone markers (Bone alkaline phosphatase (Bone ALP); C-terminal telopeptide of Type I collagen (CTX), and BMD of the spine, dual femur, forearm, and total body (DXA) were measured at baseline and after the intervention. At baseline, there were no significant group differences in strength, BMD, or bone marker variables. After 8 months of R or WBVR, there were no significant group or time effects in Bone ALP, CTX, or total body, spine, left hip or right trochanter BMD. However, right total hip and right femoral neck BMD significantly (p < 0.05) decreased in all groups. A group × time interaction (p < 0.05) was detected at radius 33% BMD site, with CON slightly increasing, and WBVR slightly decreasing. R and WBVR significantly (p < 0.05) increased 1RM strength for all exercises, while CON generally maintained strength. WBVR had significantly (p < 0.05) greater percent increases in muscular strength than R at 4 months for lat pull down, seated row, hip abduction and hip adduction and at 8 months for lat pull down, hip abduction and hip adduction. Bone metabolism in postmenopausal women was not affected by resistance training either with or without WBV. In contrast, the addition of WBV augmented the positive effects of resistance training on muscular strength in these older women.     

The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma

Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis.We examined 93 patients with DTC over 12 months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1 year.The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12 months, were − 0.88, − 1.3 and − 0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine − 2.1%, femoral neck − 2.2%, and hip − 2.1%; all P < 0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P = 0.041) and femoral neck (P = 0.010).TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period.     

Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized,Blinded, Phase 3 Trial

Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double‐blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty‐nine postmenopausal women with a T‐score ≤ ?2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one‐third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12‐mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one‐third radius; p ≤ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab‐ and alendronate‐treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.     

Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-Month,randomized, placebo-controlled,double-blind and 12-month open-label phases

This multicenter study assessed the safety and efficacy of teriparatide 20 µg/day in Japanese men and women with osteoporosis at high risk of fracture during a 12-month, randomized, double-blind, placebo-controlled treatment period followed by second and third treatment periods (to 18 and 24 months, respectively,) in which all subjects received open-label teriparatide.Subjects (93% female; median age 70 years) were randomized 2:1 to teriparatide versus placebo (randomized at baseline, teriparatide n = 137, placebo–teriparatide n = 70; entering the second period, teriparatide n = 119, placebo–teriparatide n = 59; entering the third period, teriparatide n = 102, placebo–teriparatide n = 50). For subjects with measurements at 12 months, teriparatide significantly increased bone mineral density (BMD) at the lumbar spine L2–L4 (mean percent change ± SD, teriparatide 10.04 ± 5.23% versus placebo–teriparatide 0.19 ± 4.33%), the femoral neck (teriparatide 2.01 ± 4.63% versus placebo–teriparatide 0.44 ± 3.97%), and the total hip (teriparatide 2.72 ± 4.04% versus placebo–teriparatide ? 0.26 ± 3.42%). In the placebo–teriparatide group at 24 months (12-month teriparatide dosing) BMD increased by 9.11 ± 5.14% at the lumbar spine, 2.19 ± 4.81% at the femoral neck and 2.46 ± 3.54% at the total hip. In the teriparatide group at 18 and 24 months, BMD increased from baseline at the lumbar spine by 11.93 ± 5.79% and 13.42 ± 6.12%, respectively; at the femoral neck by 2.68 ± 4.45% and 3.26 ± 4.25%, respectively; and at the total hip by 3.02 ± 3.79% and 3.67 ± 3.98%, respectively. Serum procollagen I N-terminal pro-peptide (PINP) increased rapidly with teriparatide treatment (P < 0.001 versus placebo at 1 month) and changed from baseline in the teriparatide and placebo–teriparatide groups at 12 months by a median of 78.95% and ? 17.23%, respectively, (P < 0.001) and at 24 months by 49.24% and 76.12%, respectively. The incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs were comparable in the teriparatide and placebo–teriparatide groups.These data show that teriparatide 20 µg/day was well tolerated and stimulated bone formation in Japanese subjects with osteoporosis at high risk of fracture during 18 and 24 months of treatment.     

Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: A 12-month randomized controlled trial

ObjectivesTo evaluate the effect of switching from oral bisphosphonates to denosumab on bone mineral density (BMD) in long-term glucocorticoid users.MethodsAdult patients who were receiving long-term prednisolone (≥ 2.5 mg/day for ≥ 1 year) and oral bisphosphonates (≥ 2 years) were recruited. Participants were randomized to either continue oral bisphosphonates or switch to denosumab (60 mg subcutaneously every 6 months) for 12 months. Serial BMD (lumbar spine, hip) and bone turnover markers (serum osteocalcin, P1NP, β-CTX) were measured.Results42 women were recruited (age 54.7 ± 12.9 years; 21 shifted to denosumab and 21 continued on bisphosphonates). The duration of prednisolone therapy was 101 ± 66.3 months and the daily dose was 4.4 ± 2.1 mg. Baseline demographic data, osteoporosis risk factors, and BMD at various sites were similar between the two groups of patients. At month 12, BMD of the spine and hip increased by + 3.4 ± 0.9% (p = 0.002) and + 1.4 ± 0.6% (p = 0.03), respectively, in the denosumab group; whereas the corresponding change was + 1.5 ± 0.4% (p = 0.001) and + 0.80 ± 0.5% (p = 0.12) in the bisphosphonate group. The spinal BMD at month 12 was significantly higher in the denosumab than bisphosphonate group after adjustment for baseline BMD and β-CTX values, and other confounding factors (p = 0.01). Bone turnover markers (β-CTX and P1NP) were more strongly suppressed by denosumab than the bisphosphonates. Minor infections were more common in denosumab-treated patients while other adverse events occurred at similar frequencies between the two groups.ConclusionsIn patients receiving long-term glucocorticoids, switching from oral bisphosphonates to denosumab resulted in greater gain of the spinal BMD and suppression of bone turnover markers after 12 months of therapy. The results have to be confirmed by a larger clinical trial with fracture as endpoint.     

A randomized,double-blind,multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D

This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D plus either SMC021 tablets (0.8 mg/d) or placebo for 36 months. The primary endpoint was the proportion of patients with a new vertebral fracture.The two groups were well balanced at baseline with regards to demographic and clinical data. No effect of SMC021 on preventing new vertebral fractures was observed, nor was any effect seen on new hip or non-vertebral fractures. Women receiving SMC021 had a mean 1.02% (± 0.12%) increase in lumbar spine bone mineral density (BMD) compared with a mean 0.18% (± 0.12%) increase in the placebo group by the end of the study (p < 0.0001). Similarly, small increases in BMD were observed at the femoral neck and hip in both groups. Levels of the biomarkers of bone turnover, urinary CTX-I and CTX-II, were 15% lower in the SMC021 group than in the placebo arm at 12 and 24 months, but not at 36 months. No change in quality of life between groups, assessed by the Qualeffo-14 questionnaire, was observed in either group between baseline and month 36. Pharmacokinetics analysis confirmed exposure to SMC021, but the drug levels were markedly lower than expected.Approximately 92% of subjects in each treatment group experienced an adverse event (AE), the majority of which were mild or moderate in intensity. AEs associated with SMC021 were primarily of gastrointestinal origin and included nausea, vomiting and abdominal pain, as well as hot flushes which were the reason for the slightly higher drop-out rate in the active treatment arm compared to placebo. The number of severe AEs was low in both groups. Thirty-five deaths were reported but none were considered treatment-related.Due to the lack of efficacy in preventing fractures, the development of the orally formulated calcitonin was terminated despite the promising results in earlier studies.     

Effectiveness of resistance training or jumping-exercise to increase bone mineral density in men with low bone mass: A 12-month randomized,clinical trial

PurposeTo examine the effects of 12 mo of resistance training (RT, 2 ×/wk, N = 19) or jump training (JUMP, 3 ×/wk, N = 19) on bone mineral density (BMD) and bone turnover markers (BTM) in physically active (≥ 4 h/wk) men (mean age: 44 ± 2 y; median: 44 y) with osteopenia of the hip or spine.MethodsParticipants rated pain and fatigue following each RT or JUMP session. All participants received supplemental calcium (1200 mg/d) and vitamin D (10 μg/d). BMD was measured at 0, 6, and 12 mo using DXA scans of the whole body (WB), total hip (TH) and lumbar spine (LS). BTM and 25 OHD were measured by ELISA. The effects of RT or JUMP on BMD and BTM were evaluated using 3x2 repeated measures ANOVA (time, group). This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Missouri IRB.ResultsAt baseline, 36 of 38 participants were vitamin D sufficient (25OHD > 50 nmol/L); at 12 mo, all participants were 25OHD sufficient. 25OHD did not differ between groups. WB and LS BMD significantly increased after 6 months of RT or JUMP and this increase was maintained at 12 mo; TH BMD increased only in RT. Osteocalcin increased significantly after 12 mo of RT or JUMP; CTx decreased significantly after 6 mo and returned to baseline concentrations at 12 mo in both RT and JUMP. Pain and fatigue ratings after RT or JUMP sessions were very low at 0, 6, and 12 mo.ConclusionRT or JUMP, which appeared safe and feasible, increased BMD of the whole body and lumbar spine, while RT also increased hip BMD, in moderately active, osteopenic men.     

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determined the contribution of inflammatory markers to 1-yr changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss project who were randomly assigned to 1 of 3 treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy X-ray absorptiometry and the 4% distal tibia by peripheral quantitative computed tomography. Serum inflammatory markers (C-reactive protein, interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha [TNF-α], and white blood cell count [WBC]) were measured at baseline, 6, and 12 mo. Because of attrition or missing values, data analysis at 12 mo includes only 235 women. Significant associations among IL-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1–6.1% of the variance to the observed 12-mo changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.     

Association Between Lean Mass and Handgrip Strength With Bone Mineral Density in Physically Active Postmenopausal Women

The present study evaluated 117 physically active postmenopausal women (67.8 ± 7.0 yr) who performed neuromotor physical tests (strength, balance, and mobility). Body composition (lean mass [g], fat mass [g], and % fat) and bone mineral density (BMD) of lumbar spine (L1–L4), femoral neck, and total body were measured by dual-energy X-ray absorptiometry. Following the World Health Organization criteria, osteoporosis was found in at least 1 analyzed site in 33 volunteers (28.2%): 30 (25.6%) in lumbar spine and 9 (7.7%) in femoral neck. Body weight was strongly and positively related to BMD in all sites, but the most important component of body composition was lean mass, also significantly related to all BMD sites, whereas fat mass was weakly related to the femoral neck BMD. Percent fat did not correlate with any BMD site. Of all the physical tests, the handgrip strength was most importantly related to lumbar spine, femoral neck, and total body (r = 0.49, p < 0.001; r = 0.56, p < 0.001; and r = 0.52, p < 0.001, respectively). The static body balance presented a weak but significant positive correlation only with lumbar spine. Our results suggest that strategies aiming to improve muscle strength and lean mass must contribute to the bone health of physically active postmenopausal women.     

Bone Mineral Density in Premenopausal Arab Women With Type 2 Diabetes Mellitus

IntroductionThis study compares an ethnically uniform group of premenopausal type 2 diabetic (T2DM) Arab women with a matched control group of nondiabetic subjects, in terms of their bone mineral density (BMD) and anthropometric measurements.MethodsThe study included 252 premenopausal Arab women. Their age ranged from 26 to 50 yr with a mean ± SD of 43.65 ± 8.97 yr. One hundred and twenty-two women were T2DM patients and 130 women were nondiabetic controls. The controls matched the subjects in gender, age, and body mass index (BMI). BMD was measured at total lumbar spine (L1–L4) and total left hip, using dual-energy X-ray absorptiometry (DXA; HOLOGIC, QRS SERIES, Europe, Belgium). Difference in BMD and its relationship to the anthropometric measurements in T2DM and control groups were assessed.ResultsSignificant difference was found between T2DM patients and nondiabetic patients in their mean hip BMD (0.92 ± 0.16 vs. 0.87 ± 0.14, p < 0.05) and spine BMD (0.93 ± 0.15 vs. 0.88 ± 0.14, p < 0.01). No significant difference was found in age, height, weight, and BMI (p > 0.05). The increase in hip BMD in T2DM patients normalized and the increase in spine BMD persisted after controlling for the confounding effect of age and anthropometric measurements.ConclusionPremenopausal Arab women with T2DM have higher BMD at the spine than women without T2DM. The underlying mechanism causing this increase does not seem to be related to ethnicity, gender, hormonal status, or anthropometric measurements.