Associations among endocrine,inflammatory, and bone markers,body composition and weight loss induced bone loss

IntroductionWeight loss reduces co-morbidities of obesity, but decreases bone mass.PurposeOur aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; and 3) model the contribution of these variables to post weight-loss BMD and BMC.MethodsOverweight/obese women (BMI: 28–37 kg/m²) were enrolled in an energy reduced (− 500 kcal/d; − 2092 kJ/d) diet with adequate dairy (AD: 3–4 servings/d; n = 25, 32.2 ± 8.8 years) or low dairy (LD: ≤ 1 serving/d; n = 26, 31.7 ± 8.4 years). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry.ResultsFollowing weight loss, AD intake resulted in significantly greater (p = 0.004) lumbar spine BMD and serum osteocalcin (p = 0.004) concentration compared to LD. Pre- and post-body fat was negatively associated with hip and lumbar spine BMC (r = − 0.28, p = 0.04 to − 0.45, p = 0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = − 0.29 (p = 0.04) to r = − 0.34 (p = 0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss factors. Pre-weight loss factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the factors contributed to the variance in lumbar spine BMD.ConclusionAD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone and inflammatory markers suggesting that inflammation suppresses bone metabolism. Using factor analysis, 19.6% of total variance in post-weight loss hip BMD could be explained by endocrine, immune, and anthropometric variables, but not lumbar spine BMD.     

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.     

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.     

Risedronate may preserve bone microarchitecture in breast cancer survivors on aromatase inhibitors: A randomized,controlled clinical trial

This study provides preliminary evidence that risedronate not only preserves BMD but may also attenuate the loss of bone microarchitecture over 2 years during a time of accelerated bone loss in post-menopausal breast cancer survivors on aromatase inhibitors.IntroductionAccelerated bone loss and elevated fracture risk are associated with the use of aromatase inhibitors (AIs) in women with breast cancer. We previously reported that the oral bisphosphonate, risedronate, can maintain bone mineral density (BMD) in the hip and spine over 2-years in post-menopausal breast cancer survivors on AIs. In this study, we examined whether oral bisphosphonates can also preserve bone microarchitecture as measured by the trabecular bone score (TBS) in this population.MethodsThis 2-year randomized, double-blind, placebo-controlled trial included postmenopausal women over age 55 with breast cancer on an AI who had low bone mass. Participants provided informed consent and were randomized to risedronate 35 mg once weekly or placebo. We examined 12- and 24-month changes in spine TBS, analyzed using linear mixed models.ResultsOne-hundred and nine women with a mean age of 70.5 years were included in the analysis. In the placebo group, BMD declined at the spine and hip over the 24-month period but was preserved in the active treatment group (data previously reported). TBS declined in the placebo group by − 2.1% and − 2.3% at 12- and 24-months, respectively (p < 0.005). The TBS percent change in bisphosphonate-treated patients was − 0.9% and − 1.3% at 12 and 24-months but did not reach statistical significance (p = 0.24 and 0.14). The 12- and 24-month between-group differences were 0.9 (p = 0.38) and 0.8 (p = 0.44) percentage points. TBS change correlated with spine BMD changes in the placebo group at 12- and 24-months (r = 0.33 and 0.34, p < 0.01) but not in the active treatment group.ConclusionThe oral bisphosphonate risedronate preserves BMD and may attenuate loss of bone microarchitecture over 2 years during a time of accelerated bone loss in breast cancer survivors on AIs, but more definitive evidence is needed.     

Current and past menstrual status is an important determinant of femoral neck geometry in exercising women

Menstrual status, both past and current, has been established as an important determinant of bone mineral density (BMD) in young exercising women. However, little is known regarding the association between the cumulative effect of menstrual status and indices of bone health beyond BMD, such as bone geometry and estimated bone strength.PurposeThis study explores the association between cumulative menstrual status and indices of bone health assessed using dual-energy x-ray absorptiometry (DXA), including femoral neck geometry and strength and areal BMD (aBMD), in exercising women.Methods101 exercising women (22.0 ± 0.4 years, BMI 21.0 ± 0.2 kg/m², 520 ± 40 min/week of self-reported exercise) participated in this cross-sectional study. Women were divided into three groups as follows based on their self-reported current and past menstrual status: 1) current and past regular menstrual cycles (C + P-R) (n = 23), 2) current and past irregular menstrual cycles (C + P-IR) (n = 56), 3) and current or past irregular cycles (C/P-RIR) (n = 22). Current menstrual status was confirmed using daily urinary metabolites of reproductive hormones. DXA was used to assess estimates of femoral neck geometry and strength from hip strength analysis (HSA), aBMD, and body composition. Cross-sectional moment of inertia (CSMI), cross-sectional area (CSA), strength index (SI), diameter, and section modulus (Z) were calculated at the femoral neck. Low CSMI, CSA, SI, diameter, and Z were operationally defined as values below the median. Areal BMD (g/cm²) and Z-scores were determined at the lumbar spine, femoral neck, and total hip. Low BMD was defined as a Z-score < − 1.0. Chi-square tests and multivariable logistic regression were performed to compare the prevalence and determine the odds, respectively, of low bone geometry, strength, and aBMD among groups.ResultsCumulative menstrual status was identified as a significant predictor of low femoral neck CSMI (p = 0.005), CSA (p ≤ 0.024), and diameter (p = 0.042) after controlling for confounding variables. C + P-IR or C/P-RIR were four to eight times more likely to exhibit low femoral neck CSMI or CSA when compared with C + P-R. Lumbar spine aBMD and Z-score were lower in C + P-IR when compared with C + P-R (p ≤ 0.003). A significant association between menstrual group and low aBMD was observed at the lumbar spine (p = 0.006) but not at the femoral neck or total hip (p > 0.05). However, after controlling for confounding variables, cumulative menstrual status was not a significant predictor of low aBMD.ConclusionIn exercising women, the cumulative effect of current and past menstrual irregularity appears to be an important predictor of lower estimates of femoral neck geometry, as observed by smaller CSMI and CSA, which may serve as an another means, beyond BMD, by which menstrual irregularity compromises bone strength. As such, evaluation of both current and past menstrual status is recommended to determine potential risk for relatively small bone geometry at the femoral neck.     

Racial differences in bone loss and relation to menopause among HIV-infected and uninfected women

ObjectiveTo characterize changes in bone mineral density (BMD) according to race among HIV-infected and uninfected women, and to evaluate the relationship between race and menopause-related bone loss.MethodsDual X-ray absorptiometry measured BMD on study entry and a minimum of 18 months later in 246 HIV-infected and 219 HIV-uninfected women in the Menopause Study. Linear regression analyses determined percent annual BMD change at the total hip (TH), femoral neck (FN), and lumbar spine (LS) after adjusting for potential confounders. Race-stratified and HIV-infected subgroup analyses were performed.ResultsAt baseline, mean age was 45 years, 19% of women were postmenopausal. HIV-infected women were more likely to be black (58% vs. 38%), and had lower BMI and less cigarette exposure when compared to HIV-uninfected women. Women who were perimenopausal at baseline and postmenopausal at follow-up had the greatest TH bone loss (− 1.68%/yr, p < .0001) followed by those postmenopausal throughout (− 1.02%/yr, p = .007). We found a significant interaction between HIV status and race in multivariate analyses of BMD change at the FN and TH. In race-stratified analyses, HIV infection was associated with TH BMD loss in non-black women. Black women experienced greater menopause-associated decline in TH BMD compared with non-black women.ConclusionsThe association of HIV and BMD differs strikingly by race, as do the effects of the menopausal transition on bone. Determining the extent to which the effect of HIV on fracture risk varies by race will be crucial to identify HIV-infected women at greatest risk for osteoporotic fracture, particularly as they enter menopause.     

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.     

Effect of resistance exercise on bone mineral density in premenopausal women

ObjectiveTo assess the effect of 9 months of strength training on total body and regional bone mineral density (BMD, g/cm²) in 58 premenopausal women aged 30–50 years.MethodsParticipants were randomized to either twice weekly supervised strength training for 15 weeks followed by 24 weeks of unsupervised training (treatment group) or control group. Height, weight, maximal muscular strength, nutrient intake and physical activity were assessed. Total body dual energy X-ray absorptiometry (DXA, Lunar Prodigy) scans were taken and analyzed for body composition (lean and fat mass), and BMD for total body and its sub-regions (spine, hip, arms and legs). All measurements were performed at baseline, 15 and 39 weeks. Analysis of covariance was used to assess group differences in BMD change adjusted for baseline BMD, weight, energy and calcium intake.ResultsAt baseline, the two groups had similar BMD and body size characteristics ( P < 0.05 for all), except that the treatment group had lower body weight (?7.1 kg), and higher energy (+259 kJ/d) and calcium (+232 mg/d) intake at baseline. Adjusted % change in BMD over 15 weeks (0.5% vs. 0.4%) or 39 weeks (0.9% vs. 1.2%) did not differ significantly between the exercise and control groups, respectively. The exercise group increased BMD at the spine and legs (1–2.2%), while there was no change in the controls, but differences between groups were not significant.ConclusionStrength training over 9 months did not lead to significantly greater change in total body or regional BMD in premenopausal women.     

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.     

Treinamento de força versus hidroginástica: uma análise transversal comparativa da densidade mineral óssea em mulheres na pós-menopausa

IntroductionMany studies have shown that resistance training has a positive effect on bone mineral density (BMD). However, few studies have compared the BMD of individuals undergoing resistance training and those training aquatic weight-bearing exercises.ObjectiveTo compare, in a cross-sectional study, the BMD of postmenopausal women undergoing resistance training and postmenopausal women training aquatic weight-bearing exercises.MethodsThe sample comprised 63 women divided into the following three groups: resistance training (STRENGTH: n = 15; 51.4 ± 2.7 years); aquatic weight-bearing exercises (WATER: n = 22; 54.5 ± 3.3 years); and non-trained controls (CONTROL: n = 26; 52.0 ± 3.3 years). All volunteers were on hormone replacement therapy for at least one year. The STRENGTH and WATER groups were training for at least one year prior to study beginning (mean years of training – STRENGTH: 4.5 ± 2.0; WATER: 4.2 ± 2.2).ResultsThe STRENGTH group had higher BMD of total body, femoral neck, lumbar spine L2-L4 as compared with the CONTROL group (all P < 0.05). The WATER group had higher BMD of total body, total hip, lumbar spine L2-L4 as compared with the CONTROL group (all P < 0.05). However, no difference was observed between the STRENGTH and WATER groups regarding the sites assessed.ConclusionsThose findings suggest that not only the resistance training, but also aquatic weight-bearing exercises might be a non-pharmacological strategy to prevent BMD loss in postmenopausal 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.     

Regional fat depots and their relationship to bone density and microarchitecture in young oligo-amenorrheic athletes

ContextVarious fat depots have differential effects on bone. Visceral adipose tissue (VAT) is deleterious to bone, whereas subcutaneous adipose tissue (SAT) has positive effects. Also, marrow adipose tissue (MAT), a relatively newly recognized fat depot is inversely associated with bone mineral density (BMD). Bone mass in athletes depends on many factors including gonadal steroids and muscle mass. Exercise increases muscle mass and BMD, whereas, estrogen deficiency decreases BMD. Thus, the beneficial effects of weight-bearing exercise on areal and volumetric BMD (aBMD and vBMD) in regularly menstruating (eumenorrheic) athletes (EA) are attenuated in oligo-amenorrheic athletes (OA). Of note, data regarding VAT, SAT, MAT and regional muscle mass in OA compared with EA and non-athletes (C), and their impact on bone are lacking.MethodsWe used (i) MRI to assess VAT and SAT at the L4 vertebra level, and cross-sectional muscle area (CSA) of the mid-thigh, (ii) 1H-MRS to assess MAT at L4, the proximal femoral metaphysis and mid-diaphysis, (iii) DXA to assess spine and hip aBMD, and (iv) HRpQCT to assess vBMD at the distal radius (non-weight-bearing bone) and tibia (weight-bearing bone) in 41 young women (20 OA, 10 EA and 11 C 18–25 years). All athletes engaged in weight-bearing sports for ≥ 4 h/week or ran ≥ 20 miles/week.Main outcome measuresVAT, SAT and MAT at L4; CSA of the mid-thigh; MAT at the proximal femoral metaphysis and mid-diaphysis; aBMD, vBMD and bone microarchitecture.ResultsGroups had comparable age, menarchal age, BMI, VAT, VAT/SAT and spine BMD Z-scores. EA had higher femoral neck BMD Z-scores than OA and C. Fat mass was lowest in OA. SAT was lowest in OA (p = 0.048); L4 MAT was higher in OA than EA (p = 0.03). We found inverse associations of (i) VAT/SAT with spine BMD Z-scores (r = − 0.42, p = 0.01), (ii) L4 MAT with spine and hip BMD Z-scores (r = − 0.44, p = 0.01; r = − 0.36, p = 0.02), and vBMD of the radius and tibia (r = − 0.49, p = 0.002; r = − 0.41, p = 0.01), and (iii) diaphyseal and metaphyseal MAT with vBMD of the radius (r ≤ − 0.42, p ≤ 0.01) and tibia (r ≤ − 0.34, p ≤ 0.04). In a multivariate model including VAT/SAT, L4 MAT and thigh CSA, spine and hip BMD Z-scores were predicted inversely by L4 MAT and positively by thigh CSA, and total and cortical radius and total tibial vBMD were predicted inversely by L4 MAT. VAT/SAT did not predict radius or tibia total vBMD in this model, but inversely predicted spine BMD Z-scores. When L4 MAT was replaced with diaphyseal or metaphyseal MAT in the model, diaphyseal and metaphyseal MAT did not predict aBMD Z-scores, but diaphyseal MAT inversely predicted total vBMD of the radius and tibia. These results did not change after adding percent body fat to the model.ConclusionsVAT/SAT is an inverse predictor of lumbar spine aBMD Z-scores, while L4 MAT is an independent inverse predictor of aBMD Z-scores at the spine and hip and vBMD measures at the distal tibia and radius in athletes and non-athletes. Diaphyseal MAT independently predicts vBMD measures of the distal tibia and radius.     

Associations between body mass index,lean and fat body mass and bone mineral density in middle-aged Australians: The Busselton Healthy Ageing Study

Low BMI is a risk factor for osteoporosis, but it is not clear if relationships between BMI, lean mass (LM), fat mass (FM) and BMD are consistent across different levels of BMI. We studied 1929 Caucasian participants (1014 females) aged 45–66 years in the Busselton Healthy Ageing Study in Western Australia. Body composition and BMD of total body, lumbar spine, total hip and femoral neck were measured using DXA. From generalized additive models, the positive relationships between BMI and BMD were weaker at high BMI, particularly at the spine and in males. In the entire cohort, adjusting for relevant covariates, LM and FM were significant predictors of all BMD measures in both genders. In men, analysis by tertiles of BMI showed that LM and FM (in kg) were positively associated with BMD (in mg/cm²) in tertile 1 except for LM and spine BMD (LM β: 5.18–6.80, FM β: 3.38–9.24, all P < 0.05), but not in the middle or upper tertiles (LM β: − 3.12–3.07, FM β: − 4.75–1.82, P > 0.05). In women, LM was positively associated with BMD in each tertile of BMI, except for spine BMD in the upper tertile, with regression coefficients lower in the upper tertile (β: 5.16–9.95, 5.76–9.56 and 2.80–5.78, respectively, all P < 0.05). FM was positively associated with total body, spine and total hip BMD in women in BMI tertile 1 (β: 2.86–6.68, P < 0.05); these associations were weaker or absent in the middle and upper tertiles. In conclusion, in middle-aged adults the positive relationships between lean or fat mass with BMD among those with higher BMI are absent in males and weaker in females.     

Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy

BackgroundPostmenopausal women with osteoporosis/osteopenia are at increased risk of fracture. Aromatase inhibitors further increase bone loss in these patients. This study evaluates whether zoledronic acid prevents the bone loss expected when these patients initiate letrozole.Patients and methodsPostmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a bone mineral density (BMD) T-score <?2.0 were given letrozole 2.5 mg/vitamin D 400 international units daily, calcium 500 mg twice daily, and 4 mg zoledronic acid every 6 months. The BMD was assessed at baseline and 1 year. The primary endpoint was the mean change in lumbar spine (LS) BMD at 1 year.ResultsForty-six patients completed 1 year of treatment. LS BMD increased by 2.66% (p = 0.01), femoral neck (FN) by 4.81% (p = 0.01), and any measured endpoint by 4.55% (p = 0.0052).ConclusionsZoledronic acid prevents bone loss in postmenopausal women with osteoporosis/osteopenia starting letrozole and is associated with improvements in BMD.     

Denosumab Significantly Increases DXA BMD at Both Trabecular and Cortical Sites: Results From the FREEDOM Study

Denosumab is an approved therapy for postmenopausal women with osteoporosis at high or increased risk for fracture. In the FREEDOM study, denosumab reduced fracture risk and increased bone mineral density (BMD). We report the spine and hip dual-energy X-ray absorptiometry (DXA) BMD responses from the overall study of 7808 women and from a substudy of 441 participants in which more extensive spine and hip assessments as well as additional skeletal sites were evaluated. Significant BMD improvements were observed as early as 1 mo at the lumbar spine, total hip, and trochanter (all p < 0.005 vs placebo and baseline). BMD increased progressively at the lumbar spine, total hip, femoral neck, trochanter, 1/3 radius, and total body from baseline to months 12, 24, and 36 (all p < 0.005 vs placebo and baseline). BMD gains above the least significant change of more than 3% at 36 months were observed in 90% of denosumab-treated subjects at the lumbar spine and 74% at the total hip, and gains more than 6% occurred in 77% and 38%, respectively. In conclusion, denosumab treatment resulted in significant, early, and continued BMD increases at both trabecular and cortical sites throughout the skeleton over 36 mo with important gains observed in most subjects.     

Effects of milk salt supplementation on bone mineral gain in pubertal Chinese adolescents: A 2-year randomized,double-blind,controlled, dose–response trial

Background/objectiveAdequate calcium intakes may enhance bone mineral accumulation during childhood. Little is known about the optimal calcium intake in Chinese adolescents. We examined the effects of three levels of calcium intake on bone mineral accretion in adolescents.MethodsThis was a 2-year randomized, double-blind, controlled trial. The subjects were randomly assigned to receive 40 g of milk powder containing 300 mg of calcium and 200 IU of vitamin D (Low-Ca group), or same milk powder additionally fortified with 300 mg of calcium (Mid-Ca group) or 600 mg of calcium (High-Ca group) for 2 years. The subjects' bone mineral density (BMD) and bone mineral content (BMC) at the total body, lumbar spine and left hip were determined by dual-energy X-ray absorptiometry at baseline and after the second year of treatment. Of the 111 girls and 109 boys (aged 12–14 years) enrolled, 91 girls and 91 boys completed the trial.ResultsThe girls in the High-Ca group (1,110 mg/d) had 2.3%, 2.7% and 2.6% greater BMD accretion at the total hip, femoral neck and shaft (P < 0.05) but not at total body less head and spine than those in the Low-Ca group (655 mg/d). A significant effect of higher calcium intake was also observed for percentage change of size-adjusted BMC at femur neck (P = 0.047). Bonferroni tests indicated no significant differences in the percentage changes in BMD, BMC or size-adjusted BMC between the Mid- and Low-Ca groups and between the High- and Mid-Ca groups. Extra calcium had no observable additional effect in the boys (P > 0.05).ConclusionAn intake of 1000 mg/d or more might be helpful in maximizing bone mineral accretion in the hip for girls. But further large studies are required to identify its long-term effects and the optimal calcium intake for boys.     

Low grade inflammation is associated with lower velocity of sound and broadband ultrasound attenuation in older men,but not with bone loss or fracture risk in a longitudinal aging study

ObjectivesElevated systemic levels of pro-inflammatory cytokines involved in the pathogenesis of osteoporosis. Our objective was to investigate whether low grade systemic inflammation was associated with bone markers, bone quality, bone mass and fracture risk in a population of older persons.MethodsSerum interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were measured in 1287 participants of the Longitudinal Aging Study Amsterdam (LASA), a population based study in a representative sample of older men and women (age 76 ± 6.7 years). Bone quality was measured by quantitative ultrasound measurements (QUS) at baseline and after 3 years at the calcaneus, and bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip in a subpopulation. Furthermore, the bone markers osteocalcin (OC) and urinary excretion of deoxypyridinoline (DPD) were determined. Incident clinical fractures were recorded during 6 years of follow-up.ResultsMultivariable regression analyses revealed higher IL-6 and ESR levels were associated with lower quantitative ultrasound values in older men (β = − 0.98; 95% CI − 57.72 to − 6.42, p < 0.05) and (β = − 0.221; 95% CI − 15.39 to − 3.27, p < 0.05) respectively at baseline, but not in women. No significant associations were found between inflammatory markers and bone markers, bone loss at the spine or hips, fracture rate or time to fracture.ConclusionElevated inflammatory markers are associated with impaired bone quality in older men, but not in women. No associations were found with the risk for fractures.     

Serum uric acid plays a protective role for bone loss in peri- and postmenopausal women: A longitudinal study

ObjectiveOxidative stress has been linked to osteoporosis. Serum uric acid (UA), a strong endogenous antioxidant, has been associated with higher bone mineral density (BMD), lower bone turnover and lower prevalence of fractures in a large cross-sectional study of men. Whether this relationship is present in women and how UA relates to changes in BMD longitudinally has not been examined.MethodsA sample of 356 peri- and postmenopausal women, mean age 60.5 years was studied. Each individual had baseline BMD and body composition measurements by dual energy x-ray absorptiometry (DXA) and at least one repeat measure, on average 9.7 years later. Annual rate of change in BMD (A%ΔBMD) was calculated. UA was measured at each DXA visit. Calciotropic hormones and bone turnover markers were measured at the final visit only.ResultsCross-sectional data analyses revealed that women with higher UA levels had significantly higher absolute BMD measures at all skeletal sites. These women also had higher measures of body weight and its components such as lean mass (LM) and fat mass (FM). Results of multiple regression analyses showed a positive association between UA and BMD that remained significant even after accounting for possible confounders including LM and FM. Regression analyses of the longitudinal BMD data demonstrated significant associations between serum UA levels and annual rates of change in BMD at all skeletal sites. After adjustment associations remained significant for lumbar spine, forearm and whole body BMD but not for hip BMD.ConclusionHigher serum UA levels appear to be protective for bone loss in peri- and postmenopausal women and this relationship is not affected by changes in body composition measures.     

Long-term treatment of postmenopausal osteoporosis with strontium ranelate: Results at 8 years

ObjectivesStrontium ranelate 2 g/day has proven efficacy against vertebral and nonvertebral fracture over 5 years in postmenopausal osteoporosis, though many women require longer-term treatment. This article describes the efficacy, safety, and tolerability of this agent over 8 years.MethodsPostmenopausal osteoporotic women having participated in the 5-year efficacy trials SOTI and TROPOS were invited to enter a 3-year open-label extension study. The results presented here focus on patients who received strontium ranelate for 8 years.ResultsAt the extension baseline, the population treated for 8 years (n = 879; 79.1 ± 5.6 years) had femoral neck T-score of ?2.61 ± 0.71. The cumulative incidences of new vertebral and nonvertebral fractures (13.7% and 12.0%, respectively) over years 6 to 8 were non-statistically different from the cumulative incidences in the first 3 years of the original studies (11.5% and 9.6%). Lumbar spine, femoral neck, and total hip bone mineral density (BMD) increased throughout the 8-year period. Annual relative change in BMD was significant at every visit, except the 8-year visit for femoral neck and total hip BMD. Strontium ranelate was safe and well tolerated over 8 years.ConclusionsLong-term treatment with strontium ranelate 2 g/day in postmenopausal osteoporotic women leads to continued increases in BMD at all sites. The data also provide some evidence for a sustained antifracture efficacy.     

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.