Lumbar Spine Bone Mineral Density T-score Research Articles

Finding the Optimal Resistance Training Intensity for Your Bones: Protocol for a Randomized Controlled Trial.

The purpose of this trial is to evaluate the effect of twice-weekly, moderate-to-high intensity progressive resistance training (PRT) for 1year on lumbar spine bone mineral density (BMD) in individuals with low BMD, compared to attention control. Secondary analyses will examine if resistance training improves other health outcomes; if high intensity is more effective than moderate intensity resistance training for all outcomes; the cost of intervention versus benefit; the willingness to pay; and harms. For this study, 324 men or postmenopausal women aged ≥50years with a femoral neck, total hip, or lumbar spine BMD T-score of ≤-1, or a Fracture Risk Assessment Tool probability of ≥20% for major osteoporotic fracture or ≥ 3% for hip fracture are being recruited to participate in a randomized controlled trial with 1:1:1 randomization. Participants will be stratified by site (3 centers) to twice-weekly, supervised PRT at moderate intensity (about 10 repetitions maximum), to high intensity PRT (≤6 repetitions maximum), or to a home posture and balance exercise program (attention control) for 1year (resistance training to comparator allocation ratio of 2:1). The primary outcome is lumbar spine BMD via dual-energy X-ray absorptiometry. Secondary outcomes include trabecular bone score, proximal femur and total hip BMD and structure, bone-free and appendicular lean mass, physical functioning, falls, fractures, glucose metabolism, cost per life-year gained, adverse events, and quality of life. Between-group differences will be tested in intention-to-treat and per-protocol analyses using analysis of covariance, chi-square tests, or negative binomial or logistic regression, adjusting for site and baseline values. The Finding the Optimal Resistance Training Intensity For Your Bones trial will support decision making on resistance training for people at risk of fracture.

Romosozumab is associated with greater trabecular bone score improvement compared to denosumab in postmenopausal osteoporosis.

Romosozumab significantly increases bone mineral density (BMD) and rapidly reduces fracture risk. Whether romosozumab can improve the spinal trabecular bone score (TBS) as a bone quality indicator merits further investigation. Data for postmenopausal women starting romosozumab or denosumab treatment at Severance Hospital, Korea, were analyzed. Romosozumab and denosumab groups were 1:1 matched using propensity scores, considering relevant covariates. Good responders were defined as those with TBS improvement of 5.8% or greater. Overall, 174 patients (romosozumab, n = 87; denosumab, n = 87) were analyzed. Matched groups did not differ in age (64years), weight, height, previous fracture (38%), lumbar spine or femoral neck BMD (T-score, -3.4 and -2.6, respectively), or prior bisphosphonate or selective estrogen receptor modulator (SERM) exposure (50%). The romosozumab group exhibited a greater increase in lumbar spine BMD (15.2% vs. 6.9%, p < 0.001) and TBS (3.7% vs. 1.7%, p = 0.013) than the denosumab group. In patients transitioning from bisphosphonate or SERM, romosozumab users showed greater improvement in TBS compared to denosumab users (3.9% versus 0.8%, P = 0.006); the drug-naive group showed no significant difference (3.6% versus 2.7%, P = 0.472). The romosozumab group had a higher proportion of good responders than the denosumab group (33.3% vs. 18.4%, p = 0.024). Romosozumab therapy for 12months resulted in 3.8-fold higher odds of a good response in TBS than denosumab after covariate adjustment (adjusted odds ratio 3.85, p = 0.002). Romosozumab could improve bone mass and bone quality, measured by TBS, in postmenopausal osteoporosis, particularly as a subsequent regimen in patients previously taking anti-resorptive agents.

Much lower prevalence and severity of spine degenerative changes among older Chinese women than among older Caucasian women and its implication for the interpretation of lumbar spine BMD T-score for Chinese women.

The prevalence and severity of spine degenerative changes have been noted to be lower among older Chinese women than among older Caucasian women. Spine degenerative changes associated with marginal osteophytosis, trabecular thickening, subchondral sclerosis, facet joint arthrosis, and disc space narrowing can all lead to artificially higher spine areal bone mineral density (BMD). The lower prevalence and severity of spine degeneration have important implications for the interpretation of spine areal BMD reading for Chinese women. With fewer contributions from spine degenerative changes, following natural aging, the declines of population group means of spine BMD and T-score are faster for Chinese women than for Caucasian women. While a cutpoint T-score ≤ -2.5 for defining spine densitometric osteoporosis is recommended for Caucasian women, for Chinese women the same cutpoint T-score of ≤ -2.5 inflates the estimated osteoporosis prevalence based on spine BMD measure. In addition to the use of an ethnicity-specific BMD reference database, a stricter cutpoint T-score for defining spine densitometric osteoporosis among older Chinese women should be applied.

Trabecular Bone Score Preceding and during a 2-Year Follow-Up after Sleeve Gastrectomy: Pitfalls and New Insights.

Bariatric surgery (BS) can have negative effects on bone health. Bone microarchitecture quality evaluation using the trabecular bone score (TBS) has not been described in patients after sleeve gastrectomy (SG). To test the hypothesis that the TBS is clinically useful for this population, we evaluated changes in bone mineral density (BMD) and the TBS in a longitudinal cohort study following SG. The measurements before surgery and after 12 and 24 postoperative months were as follows: weight, height, BMI, waist circumference (WC), BMD and TBS. The results at baseline showed the following: a mean BMI of 43 ± 0.56, TBS of 1.25 ± 0.02, lumbar spine BMD T-score of -0.4 ± 0.93, TBS T-score of -2.30 ± 0.21, significantly lower than BMD-T-score, and associated with a BMD-T-TBS-T gap (T-gap) of -2.05 ± 1.26 (-0.24 ± 0.13). One year after surgery, the TBS had significantly improved (+12.12% ± 1.5), leading to a T-gap of -0.296 ± 0.14, which remained stable at 2 years post-surgery. A correlation analysis revealed a significant negative correlation between the T-gap and WC (r = -0.43 p = 0.004). Our interpretation is that abdominal fat may interfere with image acquisition via increased tissue thickness, leading to a false low TBS at baseline. In conclusion, TBS should be interpreted with caution in patients with obesity and elevated WC. Additionally, we show that after SG, the LS microarchitecture measured using the TBS is partially degraded in up to 25% of patients. Further studies are warranted to assess hip bone microarchitecture changes after bariatric surgery.

Long-term effect of denosumab on bone microarchitecture as assessed by tissue thickness–adjusted trabecular bone score in postmenopausal women with osteoporosis: results from FREEDOM and its open-label extension

SummaryIn postmenopausal women with osteoporosis, up to 10 years of denosumab treatment significantly and continuously improved bone microarchitecture assessed by tissue thickness–adjusted trabecular bone score, independently of bone mineral density. Long-term denosumab treatment decreased the number of high fracture-risk patients and shifted more patients to lower fracture-risk categories.PurposeTo investigate the long-term effect of denosumab on bone microarchitecture assessed by tissue thickness–adjusted trabecular bone score (TBSTT) in post-hoc subgroup analysis of FREEDOM and open-label extension (OLE).MethodsPostmenopausal women with lumbar spine (LS) or total hip BMD T-score <−2.5 and ≥−4.0 who completed the FREEDOM DXA substudy and continued in OLE were included. Patients received either denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab; n=150) or placebo for 3 years and open-label denosumab for 7 years (crossover denosumab; n=129). BMD and TBSTT were assessed on LS DXA scans at FREEDOM baseline, month 1, and years 1–6, 8, and 10.ResultsIn long-term denosumab group, continued increases from baseline to years 4, 5, 6, 8, and 10 in BMD (11.6%, 13.7%, 15.5%, 18.5%, and 22.4%) and TBSTT (3.2%, 2.9%, 4.1%, 3.6%, and 4.7%) were observed (all P < 0.0001). Long-term denosumab treatment decreased the proportion of patients at high fracture-risk (according to TBSTT and BMD T-score) from baseline up to year 10 (93.7 to 40.4%), resulting in increases in the proportions at medium-risk (6.3 to 53.9%) and low-risk (0 to 5.7%) (P < 0.0001). Similar responses were observed in crossover denosumab group. Changes in BMD and TBSTT were poorly correlated during denosumab treatment.ConclusionIn postmenopausal women with osteoporosis, up to 10 years of denosumab significantly and continuously improved bone microarchitecture assessed by TBSTT, independently of BMD, and shifted more patients to lower fracture-risk categories.Graphical

Inflammatory Markers as a Predictor of Postmenopausal Osteoporosis

Postmenopausal osteoporosis is a progressive metabolic bone disease resulting from oestrogen deficiency. Due to the silent nature of the disease, there is an urgent need for a simple, early predictive marker. This study aimed to assess the potential of three factors-neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR)-as inflammatory markers of bone mineral density (BMD) loss. A retrospective cross-sectional study was conducted among 450 postmenopausal Omani women undergoing dual-energy X-ray absorptiometry at the Sultan Qaboos University Hospital, Muscat, Oman, from January 2017 to December 2019. The participants were allocated to groups based on lumbar spine BMD t-score values. A receiver operating characteristic curve was used to determine the area under the curve (AUC). Multivariate logistic regression was performed to identify independent predictors of low BMD. A total of 65 (14.4%), 164 (36.4%) and 221 (49.1%) women were allocated to the control, osteopenia and osteoporosis groups, respectively. No significant differences in PLR, MLR and NLR values were observed among the groups. BMD t-score values were reversely correlated with age (P = 0.007) and PLR (P = 0.004) and positively correlated with body mass index (BMI; P <0.001). The AUC was 0.59. The independent predictors of low BMD were age (>65 years) and BMI (<25 kg/m2). None of the three inflammatory biomarkers studied were found to be useful prognostic indicators of bone loss. Further research is recommended to reject or support theories regarding the role of inflammatory status in the pathogenesis.

Osteosarcopenia and type 2 diabetes mellitus in post-menopausal women: a case-control study.

Osteosarcopenia has been defined as the concomitance of low bone density (osteopenia/osteoporosis) and sarcopenia. Osteoporosis is characterized by alterations in bone microarchitecture and decrease of bone mineral density (BMD), whereas sarcopenia is the progressive decrease of both muscle mass and function that increase the risk of falls. Type 2 diabetes mellitus (T2DM) is associated with poor bone strength and muscle wasting. The aim of this study is to analyze the association between osteosarcopenia and T2DM in post-menopausal women (PMW). We performed an age matched case-control study (1:2 ratio), considering as cases PMW affected by T2DM, and PMW without T2DM as control group. For all patients a DXA evaluation to investigate bone density and body composition measures were performed. Moreover, we carried out muscle strength and performance assessments. Outcome measures were femoral neck and lumbar spine BMD T-scores, appendicular lean mass (ALM), handgrip strength and the Short Physical Performance Battery (SPPB). Data from both groups were analyzed and compared. Thirty-six PMW (12 T2DM vs 24 non-T2DM) were recruited. The frequency of osteosarcopenia was significantly higher in the T2DM group compared to controls (50% vs 17%; OR 5.0, 95% CI 1.05 to 23.79, p = 0.043). Handgrip strength was significantly lower in the T2DM group (10.09 ± 4.02 kg vs 18.40 ± 6.83 kg; p = 0.001). Post-menopausal women with T2DM have a 5 times higher risk to have osteosarcopenia compared to non-diabetic ones. Further studies on larger cohorts are required to confirm these findings.

Osteoporosis is a novel risk factor of infections and sepsis: A cohort study.

SummaryBackgroundAccumulating evidence suggests the interaction of bone metabolism and the immune system, but how bone health is associated with the risk of infections remains unknown.MethodsThis study aimed to investigate the relationship of bone mineral density (BMD) with the risk of common infections and sepsis in Hong Kong Osteoporosis Study (HKOS). A prospective cohort study, initiated in 1995 and followed until 31 December 2020, of 5,717 participants examined the association of BMD at three skeletal sites (lumbar spine, femoral neck, and total hip) with common infections - pneumonia, urinary tract infection (UTI), skin infection, and sepsis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).FindingsDuring the median follow-up of 17 years, higher BMD T-scores at the femoral neck and total hip were significantly associated with the reduced risk of pneumonia (HRs 0.89 and 0.87; 95% CIs 0.82 to 0.98 and 0.81 to 0.95), UTI (HRs 0.85 and 0.86; 95% CIs 0.76 to 0.94 and 0.78 to 0.95), skin infection (HRs 0.85 and 0.82; 95% CIs 0.74 to 0.97 and 0.73 to 0.93), and sepsis (HRs 0.83 and 0.82; 95% CIs 0.71 to 0.97 and 0.72 to 0.94). A significant association was observed for the lumbar spine BMD T-score with the risk of skin infection (HR 0.86; 95% CI: 0.78 to 0.95) but not with other infections and sepsis. Similarly, participants with osteoporosis, but not osteopenia, were significantly associated with an increased risk of infections and sepsis compared to those with normal BMD.InterpretationBMD is a novel risk factor of infections and sepsis. People with low BMD, particularly those with osteoporosis, are at higher risk of infections and sepsis than those with normal BMD. Further studies on whether improving bone health can reduce the risk of infections and sepsis are warranted.FundingNone.

The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial.

Abaloparatide significantly increased bone mineral density (BMD) in women with postmenopausal osteoporosis and decreased risk of vertebral, nonvertebral, and clinical fractures compared with placebo. The Abaloparatide for the Treatment of Men with Osteoporosis (ATOM; NCT03512262) study evaluated the efficacy and safety of abaloparatide compared with placebo in men. Eligible men aged 40 to 85 years with osteoporosis were randomized 2:1 to daily subcutaneous injections of abaloparatide 80 μg or placebo for 12months. The primary endpoint was change from baseline in lumbar spine BMD. Key secondary endpoints included BMD change from baseline at the total hip and femoral neck. A total of 228 men were randomized (abaloparatide, n= 149; placebo, n= 79). Baseline characteristics were similar across treatment groups (mean age, 68.3 years; mean lumbar spine BMD T-score, -2.1). At 12months, BMD gains were greater with abaloparatide compared with placebo at the lumbar spine (least squares mean percentage change [standard error]: 8.48 [0.54] versus 1.17 [0.72]), total hip (2.14 [0.27] versus 0.01 [0.35]), and femoral neck (2.98 [0.34] versus 0.15 [0.45]) (all p< 0.0001). The most common (≥5%) treatment-emergent adverse events were injection site reaction, dizziness, nasopharyngitis, arthralgia, bronchitis, hypertension, and headache. During 12months of abaloparatide treatment, men with osteoporosis exhibited rapid and significant improvements in BMD with a safety profile consistent with previous studies. These results suggest abaloparatide can be considered as an effective anabolic treatment option for men with osteoporosis. © 2022 Radius Health Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Evaluation of the Discrepancy in Bone Mineral Density Between the Lumbar Spine and Femoral Neck Among Japanese Women According to Age

This study aimed to examine the age-specific individual discrepancy between lumbar spine (LS) bone mineral density (BMD) and femoral neck (FN) BMD in Japanese women and to compare the significantly different characteristics between the two bone sites. We found a higher prevalence rate of discordance between the two BMD T-score sites, and many patients had a lower LS BMD T-score than FN BMD T-score. We believe that our study makes a significant contribution to the literature because our findings suggest that physicians should assess BMD more carefully in women who have a low body weight or body mass index and parental hip fracture history. For these patients, it is necessary to measure both the LS and FN BMD T-scores for calculating the fracture risk.

An Increased Bone Mineral Density As an Adverse Prognostic Factor in Patients with Systemic Mastocytosis

Systemic mastocytosis (SM) is characterized by expansion of clonal mast cells that infiltrate various organ systems. The extent of organ infiltration and subsequent organ damage distinguishes between indolent SM (ISM) and advanced SM (AdvSM). ISM patients usually present with a low mast cell burden and have a nearly normal life expectancy while AdvSM patients have a high disease burden, multiple organ damage and poor prognosis. In ISM patients, measurement of the bone mineral density (BMD) frequently reveals osteopenia and osteoporosis (lumbar spine BMD T-score of ≤ −2.5 standard deviation [SD]). In contrast, the association between increased BMD and osteosclerosis, respectively, and the various SM subtypes is unclear. We therefore sought to evaluate the BMD in 61 patients (ISM, n = 29, 48%; AdvSM, n = 32, 52%) and correlated the prevalence of osteoporosis, increased BMD and osteosclerosis with clinical parameters and prognosis. All patients were scanned on the same 16 row CT Scanner (SOMATOM Emotion 16, Siemens Healthcare Sector, Forchheim, Germany). The results were expressed as T-score (SD below the mean of young healthy adults) and as Z-score (SD below the age- and gender-matched mean reference value). According to established WHO criteria, osteoporosis was defined as a lumbar spine BMD T-score of ≤ −2.5 SD. Increased BMD and osteosclerosis were defined as Z-score &gt; 1 SD and &gt; 2 SD, respectively. Osteoporosis was detected in 11/29 (38%) patients with ISM and 2/32 (6%) patients with AdvSM (p = 0.004). Bone marrow mast cell infiltration (median 10% versus 20%, p=0.035) and serum tryptase levels (median 31 µg/L versus 58 µg/L, p = 0.047) were significantly lower in ISM patients with osteoporosis as compared to those without osteoporosis (n=18, 62%). No significant differences were seen regarding age, gender, blood counts, and overall survival. An elevated BMD was detected in 1/29 (3%) patient with ISM and 24/32 (75%) patients with AdvSM (p &lt; 0.001) while osteosclerosis was only detected in AdvSM patients (16/32, 50%). AdvSM patients with increased BMD were older (median 77 years versus 68 years, p = 0.0043), had lower platelet counts (median 111 x 109/L versus 238 x 109/L, p = 0.041) and higher levels of bone marrow mast cell infiltration (50% versus 10%, p=0.002), serum tryptase (median 262 µg/L versus 62 µg/L, p = 0.003) and alkaline phosphatase (238 U/L versus 74 U/L, p &lt; 0.0001). In consequence, prognosis of AdvSM patients with increased BMD was significantly inferior as compared to those without increased BMD (median overall survival 3.6 years versus not reached, p = 0.031). In conclusion, i) osteoporosis is a common feature in ISM but not in AdvSM patients, ii) an increased BMD is frequent in AdvSM but not in ISM patients, iii) osteosclerosis is restricted to AdvSM patients, and iv) an elevated BMD is associated with a more aggressive phenotype and inferior survival (Figure A-B). Disclosures Fabarius: Novartis: Research Funding. Reiter:Novartis: Consultancy, Honoraria, Other: Travel reimbursement, Research Funding; Blueprint: Consultancy, Honoraria, Other: Travel reimbursement; Deciphera: Consultancy, Honoraria, Other: Travel reimbursement.

Incident Fracture Risk in Type 2 Diabetic Postmenopausal Women in Mainland China: Peking Vertebral Fracture Study.

Using data from the Peking Vertebral Fracture Study, we conducted a longitudinal cohort study to investigate the association between type 2 diabetes mellitus (T2DM) and the risk of incident fractures, especially of vertebral fractures (VFs), and we also examined the modifying effect of body mass index (BMI) on this association and the effect of bone mineral density (BMD) T-score as a risk factor for incident fractures in T2DM. Chinese postmenopausal women were enrolled (n = 982), among whom 186 had T2DM. Incident VFs were confirmed by lateral radiographs of the thoracolumbar spine (T4-L5), while incident clinical non-VFs were self-reported. BMDs at the lumbar spine (LS) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry. T2DM and non-DM women were at similar risk for VFs (OR 0.74, 95% CI 0.32-1.74), even adjusting for age, BMI, BMD, and previous fractures. Meanwhile, T2DM women had nearly twice the risk for non-VFs (HR 1.95, 95% CI 1.11-3.35) compared with non-DM women. After stratifying by BMI, the risk of VFs remained similar between diabetics and non-diabetics despite their BMI status (p for interaction = 0.470), and the risk of non-VFs was positively associated with T2DM only in women with BMI ≥ 25kg/m2 (HR 3.59, 95% CI 1.68-7.65) (p for interaction = 0.065). Although LS BMD T-score was similarly and negatively associated with incident VFs both in T2DM (OR 0.34, 95% CI 0.12-0.88) and non-DM women (OR 0.60, 95% CI 0.44-0.82) (p for interaction = 0.430), the FN BMD T-score was not found to be significantly associated with either non-VFs or VFs among T2DM women. Comparing T2DM and non-DM women with similar fracture risks, the mean difference in LS T-score was - 0.36 (95% CI - 1.77 to 1.04) for VF, and difference in FN T-score was 1.61 (95% CI - 0.11 to 3.34) for non-VF. In conclusion, Chinese postmenopausal women with T2DM had a similar risk of incident VFs, but a significantly higher risk of incident non-VF, compared to women without DM. Higher BMI did not modify the effect of T2DM on risk of VFs, but it increased the association between T2DM and risk of non-VFs. LS BMD T-score was similarly and negatively associated with VF risk in T2DM and non-DM women and appear to be useful for clinical evaluation of VF risk.

The Application of PRECEDE Model on Preventing Osteoporosis in Women.

The aim of this study is investigating the efficiency of educational intervention based on PRECEDE model on promotion of osteoporosis prevention behaviors in women. This quasi-experimental study was conducted on 200 women registered in two health centers of Fasa city, Fars province, Iran in 2017 to 2018. A questionnaire including items evaluating demographic information and PRECEDE model constructs was used for measuring nutrition and walking performance of studied women in osteoporosis prevention before and 12 months after intervention. Bone mineral density (BMD) was recorded at the lumbar spine and femur before and 12 months after intervention. One year after intervention, the intervention group showed a significant increase in knowledge, attitude, self-efficacy, reinforcing factors, enabling factors, nutrition, and walking performance compared to the control group. Also, the value of lumbar spine and hip BMD T-Score of the intervention group was increased, while this value was reduced in the control group. Our findings showed that educational interventions based on PRECEDE model can positively affect prevention behaviors from osteoporosis by improving subjects' knowledge, attitude, enabling factors (resources such as health care access and services that can provide motivation for prevention behaviors from osteoporosis in women), self-efficacy, and reinforcing factors.

Stages of sarcopenia, bone mineral density, and the prevalence of osteoporosis in older women.

To assess the association between sarcopenia stages, bone mineral density (BMD), and the prevalence of osteoporosis in older women. Two hundred thirty-four women (68.3 ± 6.3years) underwent body composition and BMD measurements using dual-energy X-ray absorptiometry. Quadriceps isokinetic torque was evaluated, and the timed up-and-go test was conducted as a measure of function. Sarcopenia stages were classified according to European Working Group on Sarcopenia in Older People (EWGSOP): nonsarcopenia, presarcopenia, sarcopenia, and severe sarcopenia. Osteoporosis was defined as BMD value (hip or spine) 2.5 standard deviations below a young-adult reference population. Between-group differences were examined using ANOVA for continuous variables and chi-squared for categorical variables. Logistic regression was performed to evaluate the association between sarcopenia stages and osteoporosis. Rates of osteoporosis were 15.8%, 19.2%, 35.3%, and 46.2% for nonsarcopenia, presarcopenia, sarcopenia, and severe sarcopenia, respectively (P = 0.002). Whole-body and femoral neck BMD values were significantly lower among all sarcopenia stages when compared to nonsarcopenia (all P values < 0.05, η2p 0.113 to 0.109). The severe sarcopenia group also showed significantly lower lumbar spine BMD values and T-scores (both P values < 0.05; η2p 0.035 and 0.037, respectively). When clustered, sarcopenia and severe sarcopenia exhibited lower BMD values for all sites (all P values < 0.01), and presented a significantly higher risk for osteoporosis (odds ratio 3.445; 95% CI 1.521-7.844). The observed results provide support for the concept that a dose-response relationship exists between sarcopenia stages, BMD, and the presence of osteoporosis. These findings strengthen the clinical significance of the EWGSOP sarcopenia definition and indicate that severe sarcopenia should be viewed with attention by healthcare professionals.

Postmenopausal osteoporosis is associated with elevated aldosterone/renin ratio.

Plasma aldosterone/renin ratio (ARR) is a useful method for primary aldosteronism (PA) screening. However some confounders, such as medications and dietary, affect plasma renin and aldosterone levels, resulting in false-negative or -positive plasma ARR. This study investigated the association between postmenopausal osteoporosis (PMO) and plasma ARR. Bone mineral density (BMD) was measured by dual-energy X-ray-absorptiometry (DXA) in 324 normotensive postmenopausal women. Based on clinical characteristics and BMD, 186 and 96 subjects were diagnosed as PMO and osteopenia respectively, and the remaining 42 subjects were grouped as normal BMD. Plasma aldosterone concentration (PAC), plasma renin concentration (PRC), parathyroid hormone (PTH), bone alkaline phosphatase (BALP) and 25-Hydroxyvitamin D(25-(OH)D) were determined. Subjects with PMO showed significantly higher levels of PAC (121.0 ± 78.8 vs. 81.8 ± 71.5 pg/ml, p < 0.01 and 121.0 ± 78.8 vs. 91.7 ± 56.2 pg/ml, p < 0.01) and ARR (32.0 ± 53.6 vs. 9.0 ± 9.3 pg/μU, p < 0.01 and 32.0 ± 53.6 vs. 16.3 ± 32.1 pg/μU, p < 0.01) compared to women with normal BMD and osteopenia, respectively. Using ARR ≥ 37.0 pg/μU as the cutoff for positive screening, more false-positive was found in the PMO group when compared to the normal BMD group (24 vs. 2%) and osteopenia group (24 vs. 7%), respectively. PAC was negatively associated with lumbar spine BMD T-score (r = -0.239, p < 0.001), femur neck BMD T-score (r = -0.234, p < 0.001) and total hip BMD T-score (r = -0.228, p < 0.001). PTH was positively associated with PAC (r = 0.119, p < 0.05) and ARR (r = 0.136, p < 0.05). PAC and ARR are elevated in women with PMO, which might increase the risk of false-positive for case detection of PA.

Mechanisms of Enhanced Osteoclastogenesis in Alkaptonuria

Alkaptonuria (AKU) is a rare disorder characterized by the deficiency of the enzyme homogentisate 1,2-dioxygenase and consequent homogentisate accumulation, which leads to progressive and severe osteoarthopathy starting from the second decade of life. Thus, in AKU patients, bone involvement represents an important clinical issue, which we investigated. Serum levels of receptor activator of NF-κB ligand (RANKL), osteoprotegerin, sclerostin, Dickkopf-1, and bone remodeling markers were measured in nine AKU patients (two children and seven adults) and 22 controls, together with lumbar spine bone mineral density (LS-BMD) and femoral-BMD. In the two AKU children, the average of LS-BMD and femoral-BMD Z-scores were within the normal range, but reduced with respect to the controls. Otherwise, in the adult AKU patients, LS-BMD T-score was inside the normal range, but femoral-BMD T-score reached osteopenic levels. Consistently, in AKU adults, higher RANKL and C-terminal telopeptide of collagen type 1 and lower osteoprotegerin levels were observed than in controls. Otherwise, spontaneous osteoclastogenesis was already evident in peripheral blood mononuclear cell cultures from AKU children, together with a high percentage of circulating osteoclast precursors. Osteoclastogenesis was sustained by the high levels of tumor necrosis factor-α, RANK, RANKL, and LIGHT. In conclusion, the altered osteoclastogenesis was observed already in AKU children, despite the absence of evident injury. Thus, a preventive approach in young patients, targeting osteoclast activity, may prevent the macroscopic bone disease that appears in adult AKU.

Effect of denosumab on trabecular bone score in postmenopausal women with osteoporosis.

TBS, a gray-level texture index determined from lumbar spine DXA scans, correlates with bone microarchitecture and enhances assessment of vertebral fracture risk independently of BMD. In the FREEDOM study, denosumab increased BMD and reduced new vertebral fractures in postmenopausal women with osteoporosis. This retrospective analysis explored the effect of denosumab on TBS and the association between TBS and BMD in FREEDOM. Postmenopausal women with lumbar spine or total hip BMD T-score <-2.5 and -4.0 or higher at both sites received placebo or denosumab 60mg subcutaneously every 6months. TBS indices were determined from DXA scans at baseline and months 12, 24, and 36 in a subset of 285 women (128 placebo, 157 denosumab) who had TBS values at baseline and ≥1 postbaseline visit. Baseline characteristics were comparable between treatment groups; mean (SD) lumbar spine BMD T-score was -2.79 (0.64), and mean (standard deviation [SD]) TBS was 1.200 (0.101) overall. In the placebo group, BMD and TBS increased by ≤0.2% or decreased from baseline at each visit. In the denosumab group, progressive increases from baseline at 12, 24, and 36months were observed for BMD (5.7, 7.8, and 9.8%) and TBS (1.4, 1.9, and 2.4%). Percentage changes in TBS were statistically significant compared with baseline (p<0.001) and placebo (p≤0.014). TBS was largely unrelated to BMD, regardless of treatment, either at baseline or for annual changes from baseline (all r 2≤0.06). In postmenopausal women with osteoporosis, denosumab significantly improved TBS independently of BMD.

Psoriasis, fracture risk and bone mineral density: the HUNT Study, Norway.

An association between psoriasis and osteoporosis has been reported. To investigate, in a large prospective population-based Norwegian study, whether psoriasis is associated with increased risk of forearm or hip fracture; to investigate the cross-sectional association between psoriasis and bone mineral density (BMD) T-score in a subpopulation. Hospital-derived fracture data from Nord-Trøndelag County (1995-2013) were linked to psoriasis information, BMD measurements and lifestyle factors from the third survey of the Nord-Trøndelag Health Study 2006-08 (HUNT3); socioeconomic data from the National Education Database; and use of medication from the Norwegian Prescription Database. Among 48 194 participants in HUNT3, we found no increased risk of forearm or hip fracture in 2804 patients with self-reported psoriasis [overall age- and sex-adjusted hazard ratio 1·03, 95% confidence interval (CI) 0·82-1·31]. No clear association was found between psoriasis and mean BMD T-score; overall age- and sex-adjusted differences in total hip, femoral neck and lumbar spine BMD T-scores were 0·02 (95% CI -0·11 to 0·14), 0·05 (95% CI -0·06 to 0·17) and 0·07 (95% CI -0·09 to 0·24), respectively. No clear association was found between psoriasis and prevalent osteoporosis in either total hip, femoral neck or lumbar spine; overall age- and sex-adjusted odds ratio was 0·77 (95% CI 0·54-1·10). Associations did not change substantially after adjustment for education, smoking, systemic steroid use and body mass index. We found no association between psoriasis and risk of fracture. The study did not indicate reduced BMD T-score or higher prevalence of osteoporosis among patients with psoriasis.

Relationship between baseline characteristics and response to risedronate treatment for osteoporosis: data from three Japanese phase III trials

SummaryWe evaluated the influence of baseline age, bone mineral density (BMD), and serum levels of vitamin D on the response to risedronate treatment. Risedronate consistently increased BMD, but our results suggest vitamin D supplementation may be necessary to achieve optimal treatment effect. Furthermore, early intervention may help prevent bone fractures.IntroductionWe aimed to investigate the influence of baseline age, BMD, and vitamin D insufficiency on the response to risedronate treatment.MethodsData regarding 1447 patients was obtained from the registries of three phase III clinical trials of risedronate. The response to treatment was expressed in terms of BMD increase and occurrence of new vertebral fractures. The patients were stratified by baseline values for age (<65, 65–72, and ≥72 years), lumbar spine BMD T-score (osteoporotic, <−2.5; and non-osteoporotic, ≥− 2.5), and serum levels of 25-hydroxyvitamin D (deficient, <21 ng/mL; and non-deficient, ≥21 ng/mL).ResultsRisedronate consistently increased lumbar spine BMD in all the groups, with similar percentage and absolute increments in all the age tertiles. The percentage, but not absolute, increment in BMD was significantly higher (p = 0.0003) in the osteoporotic than that in the non-osteoporotic patients (baseline). Of the 1330 patients whose baseline serum levels of 25-hydroxyvitamin D were available, 44.7% had vitamin D deficiency (<20 ng/mL), while 89.2% had insufficiency (<30 ng/mL). The percentage and absolute increments in BMD were lower (p < 0.05 and p < 0.01, respectively) in the vitamin D-deficient than those in the non-deficient patients. New vertebral fractures occurred in 1.5 and 0.8% of the osteoporotic and non-osteoporotic patients, respectively (end of the treatment).ConclusionsTherapeutic response in elderly patients is consistent, but early initiation of risedronate treatment may help prevent fractures. Risedronate-induced increase in BMD is lower in patients with vitamin D deficiency, suggesting that vitamin D supplementation is important to achieve optimal treatment response.

Effects of short-term step aerobics exercise on bone metabolism and functional fitness in postmenopausal women with low bone mass.

The major goal of this study was to determine the effects of short-term group-based step aerobics (GBSA) exercise on the bone metabolism, bone mineral density (BMD), and functional fitness of postmenopausal women (PMW) with low bone mass. Forty-eight PMW (aged 58.2±3.5years) with low bone mass (lumbar spine BMD T-score of -2.00±0.67) were recruited and randomly assigned to an exercise group (EG) or to a control group (CG). Participants from the EG attended a progressive 10-week GBSA exercise at an intensity of 75-85% of heart rate reserve, 90min per session, and three sessions per week. Serum bone metabolic markers (C-terminal telopeptide of type 1 collagen [CTX] and osteocalcin), BMD, and functional fitness components were measured before and after the training program. Mixed-models repeated measures method was used to compare differences between the groups (α=0.05). After the 10-week intervention period, there was no significant exercise program by time interaction for CTX; however, the percent change for CTX was significantly different between the groups (EG=-13.1±24.4% vs. CG=11.0±51.5%, P<0.05). While there was no significant change of osteocalcin in both groups. As expected, there was no significant change of BMD in both groups. In addition, the functional fitness components in the EG were significantly improved, as demonstrated by substantial enhancement in both lower- and upper-limb muscular strength and cardiovascular endurance (P<0.05). The current short-term GBSA exercise benefited to bone metabolism and general health by significantly reduced bone resorption activity and improved functional fitness in PMW with low bone mass. This suggested GBSA could be adopted as a form of group-based exercise for senior community.