Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis.

BACKGROUND: Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. METHODS: In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. RESULTS: Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and ß-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment. CONCLUSION: Our results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

MRI Quantification of Cortical Bone Porosity, Mineralization, and Morphologic Structure in Postmenopausal Osteoporosis.

Background Preclinical studies have suggested that solid-state MRI markers of cortical bone porosity, morphologic structure, mineralization, and osteoid density are useful measures of bone health. Purpose To explore whether MRI markers of cortical bone porosity, morphologic structure, mineralization, and osteoid density are affected in postmenopausal osteoporosis (OP) and to examine associations between MRI markers and bone mineral density (BMD) in postmenopausal women. Materials and Methods In this single-center study, postmenopausal women were prospectively recruited from January 2019 to October 2020 into two groups: participants with OP who had not undergone treatment, defined as having any dual-energy x-ray absorptiometry (DXA) T-score of -2.5 or less, and age-matched control participants without OP (hereafter, non-OP). Participants underwent MRI in the midtibia, along with DXA in the hip and spine, and peripheral quantitative CT in the midtibia. Specifically, MRI measures of cortical bone porosity (pore water and total water), osteoid density (bound water [BW]), morphologic structure (cortical bone thickness), and mineralization (phosphorous [P] density [31P] and 31P-to-BW concentration ratio) were quantified at 3.0 T. MRI measures were compared between OP and non-OP groups and correlations with BMD were assessed. Results Fifteen participants with OP (mean age, 63 years ± 5 [SD]) and 19 participants without OP (mean age, 65 years ± 6) were evaluated. The OP group had elevated pore water (11.6 mol/L vs 9.5 mol/L; P = .007) and total water densities (21.2 mol/L vs 19.7 mol/L; P = .03), and had lower cortical bone thickness (4.8 mm vs 5.6 mm; P < .001) and 31P density (6.4 mol/L vs 7.5 mol/L; P = .01) than the non-OP group, respectively, although there was no evidence of a difference in BW or 31P-to-BW concentration ratio. Pore and total water densities were inversely associated with DXA and peripheral quantitative CT BMD (P < .001), whereas cortical bone thickness and 31P density were positively associated with DXA and peripheral quantitative CT BMD (P = .01). BW, 31P density, and 31P-to-BW concentration ratio were positively associated with DXA (P < .05), but not with peripheral quantitative CT. Conclusion Solid-state MRI of cortical bone was able to help detect potential impairments in parameters reflecting porosity, morphologic structure, and mineralization in postmenopausal osteoporosis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bae in this issue.

Associations of long chain polyunsaturated fatty acids with bone mineral density and bone turnover in postmenopausal women.

PURPOSE: The immunomodulatory properties of n-3 long chain polyunsaturated fatty acids (LCPUFA) are reported to reduce bone loss through alteration of bone remodelling and n-3 LCPUFA, therefore, may benefit bone health in post-menopausal women, a vulnerable group at high risk of osteoporosis. METHODS: Measures of bone mineral density (BMD) were determined using dual energy X-ray absorptiometry (DEXA) in 300 post-menopausal women. The bone turnover markers osteocalcin (OC), C-terminal telopeptides of type 1 collagen (CTX) and total alkaline phosphatase were quantified in serum along with urinary creatinine corrected deoxypyridinoline (DPD/Cr) and CTX/Cr and the CTX:OC ratio calculated. Total serum n-6 PUFA (LA + AA) and n - 3 LCPUFA (ALA + EPA + DPA + DHA) were measured and the n - 6:n - 3 ratio was calculated. RESULTS: Mean (SD) age and body mass index (BMI) were 61 (6.4) years and 27.4 (4.8) kg/m2, respectively with participants being 12.6 (7.6) years post-menopause. Multiple regression analysis identified no association between n-3 LCPUFA and any of the measures of T-score or BMD albeit a significant positive association between total n - 3 LCPUFA and femur BMD (ß = 0.287; p = 0.043) was observed within those women with a low n - 6:n - 3 ratio. There was a significant inverse association between ALA and urinary DPD/Cr (ß = - 0.141; p = 0.016). CONCLUSION: A favourable low n - 6:n - 3 ratio was associated with higher femur BMD and a higher n - 3 LCPUFA (ALA) was associated with lower bone resorption. These results support a beneficial role for n - 3 LCPUFA in reducing postmenopausal bone resorption and favourably influencing BMD. TRIAL NUMBER & DATE OF REGISTRATION: ISRCTN63118444, 2nd October 2009, "Retrospectively registered".

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study.

PURPOSE: The effects of daily teriparatide (20 µg) (D-PTH), weekly high-dose teriparatide (56.5 µg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients. METHODS: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months' treatment compared with baseline. RESULTS: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (-4.1%, -3.0%, -1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (-1.8%, -0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (-0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (-0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%). CONCLUSIONS: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH.

Characteristics of Long-Term Femoral Neck Bone Loss in Postmenopausal Women: A 25-Year Follow-Up.

The aim of this study was to monitor long-term changes in bone mineral density (BMD) after menopause and factors affecting BMD. The study population consisted of a random sample of 3222 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study, of which 62.1% were postmenopausal at the beginning of the study. This group of women underwent dual-energy X-ray absorptiometry (DXA) measurements at the femoral neck every 5 years from baseline (in 1989) up to 25-year follow-up. They also responded to risk-factor questionnaires at 5-year intervals. During the 25-year follow-up, the baseline cohort decreased to 686 women. The women were divided into quartiles based on their baseline BMD. Self-reported hormone replacement therapy (HRT) and corticosteroid use were divided into ever users and never users. Morbidity was assessed as the total number of self-reported diseases and BMD-affecting diseases. The mean 25-year BMD change was found to be -10.1%, p < 0.001. Higher baseline BMD was associated with higher bone loss rate; the reduction in the highest quartile BMD was 11.1% and in the lowest quartile 7.4% (p = 0.0031). Lower baseline body mass index (BMI) and a greater increase in BMI were found to protect against postmenopausal bone loss (p < 0.001). The lowest bone loss quartile included 15.2% more HRT users than the highest bone loss quartile (p = 0.004). The number of diseases/bone-affecting diseases, use of vitamin D/calcium supplementation, use of corticosteroids, smoking or alcohol use had no statistical significance for annual bone loss rate. This study presents hitherto the longest (25-year) BMD follow-up in postmenopausal women. The linear femoral neck bone loss of 10% was less than previously assumed. A 5-year BMD change appeared to predict long-term bone loss in postmenopausal women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effects of Melandrium firmum Rohrbach on RANKL­induced osteoclast differentiation and OVX rats.

Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density (BMD), which results in an increased risk of fracture. Melandrium firmum (Siebold & Zucc.) Rohrbach (MFR), 'Wangbulryuhaeng' in Korean, is the dried aerial portion of Melandrii Herba Rohrbach, which is a member of the Caryophyllaceae family and has been used to treat several gynecological conditions as a traditional medicine. However, to the best of our knowledge, the effect of MFR on osteoclast differentiation and osteoporosis has not been assessed. To evaluate the effects of MFR on osteoclast differentiation, tartrate­resistant acid phosphatase staining, actin ring formation and bone resorption assays were used. Additionally, receptor activator of nuclear factor­κB ligand­induced expression of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) and c­Fos were measured using western blotting and reverse transcription­PCR. The expression levels of osteoclast­related genes were also examined. To further investigate the anti­osteoporotic effects of MFR in vivo, an ovariectomized (OVX) rat model of menopausal osteoporosis was established. Subsequently, the femoral head was scanned using micro­computed tomography. The results revealed that MFR suppressed osteoclast differentiation, formation and function. Specifically, MFR reduced the expression levels of osteoclast­related genes by downregulating transcription factors, such as NFATc1 and c­Fos. Consistent with the in vitro results, administration of MFR water extract to OVX rats reduced BMD loss, and reduced the expression levels of NFATc1 and cathepsin K in the femoral head. In conclusion, MFR may contribute to alleviate osteoporosis­like symptoms. These results suggested that MFR may exhibit potential for the prevention and treatment of postmenopausal osteoporosis.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

CONTEXT: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. OBJECTIVE: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. DESIGN AND METHODS: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. RESULTS: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 µM). CONCLUSIONS: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

Comprehensive evaluation of the combined extracts of Epimedii Folium and Ligustri Lucidi Fructus for PMOP in ovariectomized rats based on MLP-ANN methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Kidney deficiency is the main pathogenesis of osteoporosis based on the theory of "kidney governing bones" in traditional Chinese medicine (TCM). Osteoporosis is a systemic disease; kidney deficiency influences the growth, aging and reproduction of human body, reflecting in endocrine, nerve, immunity, metabolism and other functions. Multi-target drugs composed of natural non-toxic products from kidney-reinforcing herbs, are being investigated for the treatment of osteoporosis. Therefore, it is necessary and imperative to develop an objective and comprehensive method to evaluate and compare the effects of herbs with listed drugs. AIM OF THE STUDY: This study was designed to evaluate and compare the therapeutic effects and the underlying molecular mechanism of the combined extracts of Epimedii Folium and Ligustri Lucidi Fructus (EL) with Raloxifene hydrochloride (RH) in ovariectomy (OVX)-induced postmenopausal osteoporosis (PMOP) rats based on the multi-layer perception (MLP)-artificial neural network (ANN) model. MATERIALS AND METHODS: Female SD rats were subjected to either sham surgery (n = 8) or bilateral OVX (n = 48). One week after recovering from surgery, the OVX-induced rats were randomly divided into three groups: OVX model group (n = 32, every 8 rats were killed at the end of the 5th, 9th, 11th or 13th week after OVX), EL group (treated with EL 0.35 g/kg, n = 8), and RH group (treated with RH 6.25 mg/kg, n = 8). The rats in the treatment groups were administrated once a day for 12 weeks, then sacrificed. We observed bone mass and quality, bone remodeling, the function of estrogen and TGF-ß1/Smads pathway in all rats. RESULTS: Both EL and RH could increase bone mineral density, enhance bone strength, relieve bone micro-structure degeneration, re-balance bone remodeling, regulate estrogen dysfunction, and up-regulate TGF-ß1 expression. The evaluation of the MLP-ANN model showed that EL and RH had markedly anti-PMOP effects, and there was no significant difference in the comprehensive evaluation of anti-osteoporosis between the two drugs. However, RH had better effects on bone mass and quality and TGF-ß1/Smads pathway than EL; EL had better effects on estrogen function than RH. CONCLUSION: Combined extracts of Epimedii Folium and Ligustri Lucidi Fructus (EL) exhibited bone-protective effects on PMOP. The MLP-ANN method evaluated the efficacy of drugs more comprehensively, which provided a new direction for the evaluation and comparison of drugs.

Effects of Gushukang for postmenopausal osteoporosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Postmenopausal osteoporosis (PMO) is one of the most common systemic bone diseases with a high risk of fracture. Traditional herbal formula Gushukang (GSK) has been used to treat PMO. However, there is no systematic review related to GSK for PMO. The object of this work is to evaluate the efficacy and safety of GSK in the management of PMO. METHODS: We will search the PubMed, Embase, MEDLINE, Cochrane Library Central Register of Controlled Trials, China national knowledge infrastructure database (CNKI), Wan fang database, Chongqing VIP information, and SinoMed from their inception to May 2020. All randomized controlled trials (RCTs) of GSK for the treatment of PMO will be included. The improvement of vertebral fracture and bone mineral density (BMD) will be accepted as the primary outcomes. The meta-analyses will be performed by using the RevMan 5.3. RESULTS: This study will provide a high-quality comprehensive evaluation of the efficacy and safety of GSK for treating patients with PMO. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether GSK is an effective intervention for patients with PMO. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/MKN3F.

Feasibility of an interprofessional collaborative osteoporosis screening programme in Malaysia.

Background Population screening for osteoporosis using bone mineral density scan is not feasible in Malaysia as this test is costly. Hence, there is a need to develop a more efficient method to screen for osteoporosis.Objectives To determine the feasibility of an interprofessional collaborative osteoporosis screening programme (IPC-OSP). Methods Postmenopausal women aged ≥ 50 years, who had not been diagnosed with osteoporosis were recruited from a primary care clinic from June to August 2014. Patients were assessed for their osteoporosis risk and were counselled on prevention methods. Patients at risk were referred to the doctor with a recommendation for a bone mineral density (BMD) scan. Results Fifty out of 55 patients were recruited (response rate = 90.9%). A total 26/50 (52.0%) went for a bone mineral density scan, none were osteoporotic, 17/50 (34%) were osteopenic, 2/50 (4.0%), were started on osteoporosis medications and 14/50 (28%) modified their lifestyle to improve bone health or started on calcium supplements. Osteoporosis knowledge significantly increased from baseline to month two (46.3 ± 21.4 vs. 79.1 ± 14.3, p < 0.001). Patients had a satisfaction score of 89.8 ± 12.4. Follow-up rates were 83.9% and 100% at months 1 (BMD appointment) and 2 (phone follow up), respectively. The intervention was successfully coordinated. Data entry was determined to be viable based on the researchers' experience. Conclusion The interprofessional collaborative osteoporosis screening programme was found to be feasible in Malaysia.

Trabecular Bone Score Is a Useful Parameter for the Prediction of Vertebral Fractures in Patients With Polymyalgia Rheumatica.

INTRODUCTION: Polymyalgia rheumatica (PMR), a benign rheumatic disorder, requires long-term glucocorticoid therapy, which could be associated with osteoporosis. In the present study, we compared bone mineral density (BMD), trabecular bone score (TBS) and frequencies of vertebral fracture (VF) among patients with PMR or rheumatoid arthritis (RA) and controls. METHODS: Fifty-three postmenopausal women with PMR aged 50 yr or older were eligible for inclusion in this study. Subjects in RA (n = 106) and control (n = 106) groups were selected by propensity score matching with controlling age, body mass index and use of anti-osteoporotic agents. RESULTS: The frequency of VF in patients with PMR (30.2%) was significantly higher than those in patients with RA (13.2 %) and controls (13.2%, p = 0.017). The mean TBS of patients with PMR (1.317 ± 0.092) was significantly lower than those of patients with RA (1.336 ± 0.089) and the controls (1.373 ± 0.073, p < 0.001). In receiver operating characteristic analysis for VF in patients with PMR, the area under the curve (AUC) was 0.759 (95% confidence interval [CI] = 0.601-0.918, p < 0.001) for TBS and 0.618 (95% CI = 0.442-0.795, p < 0.001) for L-spine BMD. The AUCs were 0.760 (95% CI = 0.630-0.891, p ≤ 0.001) and 0.767 (95% CI 0.627-0.907, p < 0.001) for femur neck and total hip BMD, respectively. Multivariate analysis identified the factor associated with VF of patients with PMR as a lower TBS (Odds ratio: 0.000, 95% CI: 0.000, 0.754, p = 0.043). CONCLUSION: TBS could be a supplementary tool for discriminating osteoporotic fractures in postmenopausal patients with PMR.

Anti-osteoporotic and Anti-adipogenic Effects of Rhus chinensis Nutgalls in Ovariectomized Mice Fed with a High-fat Diet.

In traditional oriental medicine, nutgalls of Rhus chinensis have been used to treat various gastrointestinal and respiratory disorders. This study aimed to investigate the benefits of nutgalls of R. chinensis on bone loss and obesity in ovariectomized mice fed with a high-fat diet. Following surgical menopause induction, nutgalls of R. chinensis was orally administered for 4 weeks. Body weight gain and organ weights were measured. Histopathological examinations and UHPLC-MS/MS analysis were performed. Nutgalls of R. chinensis remarkably decreased obesity, gonadal fat, and bone loss in ovariectomized mice fed with a high-fat diet. Nutgalls of R. chinensis inhibited adipocyte differentiation of multipotent bone marrow stromal cells and reduced fat accumulation in gonadal fat, liver, and bone tissues. In UHPLC-MS/MS analysis, 27 phytochemicals containing gallotannin derivatives and flavonoids were identified by comparison with mass fragmentation of authentic standards. Taken together, the results demonstrate the beneficial effects of nutgalls of R. chinensis and its phytochemicals to manage postmenopausal bone disorders and obesity.

Trabecular bone score and quantitative ultrasound measurements in the assessment of bone health in breast cancer survivors assuming aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AIs) represent the first-line adjuvant therapy for hormone receptor-positive breast cancer (BC) women. AIs have been associated with an increased rate of fractures. The aim of our study was to investigate trabecular bone score (TBS) and bone quantitative ultrasound (QUS) measurements as bone quality surrogates in AIs users. METHODS: Sixty postmenopausal BC women starting AIs and forty-two controls (mean age 61.64 ± 8.33 years) were considered. Bone mineral density (BMD) at lumbar spine and femoral neck and TBS were measured by DXA; QUS-derived Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), and Ultrasound Bone Profile Index (UBPI) were assessed at phalangeal site; morphometric vertebral fractures (Vfx) by X-ray, serum bone-specific alkaline phosphatase (BSAP), and C-telopeptide of type 1 collagen (CTX) were also evaluated. RESULTS: After 18 months, changes of TBS vs baseline were significantly different between AIs group and controls [Δ TBS - 2.2% vs - 0.4%, respectively, p = 0.001]. AD-SoS, BTT and UBPI values decreased only in AIs' group (- 3.7%, - 6.45%, -8.5%, vs baseline, respectively, pall < 0.001). 3 Vfx occurred in AIs users and were associated with the greater TBS and AD-SoS modifications. In the AIs' group, ΔTBS was associated with ΔAD-SoS (r = 0.58, p < 0.001) and ΔUBPI (r = 0.415, p = 0.001), but not with ΔBMD. Moreover, ΔTBS was independently predicted by ΔAD-SoS, after correcting for BMD, CTX and BSAP level changes (ß = 0.37, SE = 2.44, p < 0.001). CONCLUSIONS: TBS and phalangeal QUS provide useful information related to bone quality in AI-treated BC survivors and could be considered for fracture risk evaluation.

Magnetic resonance imaging T1 and T2 mapping provide complementary information on the bone mineral density regarding cancellous bone strength in the femoral head of postmenopausal women with osteoarthritis.

BACKGROUND: Since bone mass is not the only determinant of bone strength, there has been increasing interest in incorporating the bone quality into fracture risk assessments. We aimed to examine whether the magnetic resonance imaging (MRI) T1 or T2 mapping value could provide information that is complementary to bone mineral density for more accurate prediction of cancellous bone strength. METHODS: Four postmenopausal women with hip osteoarthritis underwent 3.0-T MRI to acquire the T1 and T2 values of the cancellous bone of the femoral head before total hip arthroplasty. After the surgery, the excised femoral head was portioned into multiple cubic cancellous bone specimens with side of 5 mm, and the specimens were then subjected to microcomputed tomography followed by biomechanical testing. FINDINGS: The T1 value positively correlated with the yield stress (σy) and collapsed stress (σc). The T2 value did not correlate with the yield stress, but it correlated with the collapsed stress and strength reduction ratio (σc/σy), which reflects the progressive re-fracture risk. Partial correlation coefficient analyses, after adjusting for the bone mineral density, showed a statistically significant correlation between T1 value and yield stress. The use of multiple coefficients of determination by least squares analysis emphasizes the superiority of combining the bone mineral density and the MRI mapping values in predicting the cancellous bone strength compared with the bone mineral density-based prediction alone. INTERPRETATION: The MRI T1 and T2 values predict cancellous bone strength including the change in bone quality.

Lipoprotein(a) plasma levels, bone mineral density and risk of hip fracture: a post hoc analysis of the Women's Health Initiative, USA.

OBJECTIVES: Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women. DESIGN: Post hoc analysis of data from the Women's Health Initiative (WHI), USA. SETTING: 40 clinical centres in the USA. PARTICIPANTS: The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast and colorectal cancers and osteoporotic fractures among postmenopausal women. Recruitment for WHI took place from 1 October 1993 to 31 December 1998. EXPOSURES: Plasma Lp(a) levels were measured at baseline. OUTCOME MEASURES: Incident hip fractures were ascertained annually and confirmed by medical records with follow-up through 29 August 2014. BMD at the femoral neck was measured by dual X-ray absorptiometry in a subset of participants at baseline. STATISTICAL ANALYSES: Cox proportional hazards and logistic regression models were used to evaluate associations of quartiles of plasma Lp(a) levels with hip fracture events and hip BMD T-score, respectively. RESULTS: During a mean follow-up of 13.8 years, 454 incident cases of hip fracture were observed. In analyses adjusting for confounding variables including age, body mass index, history of hysterectomy, smoking, physical activity, diabetes mellitus, general health status, cardiovascular disease, use of menopausal hormone therapy, use of bisphosphonates, calcitonin or selective-oestrogen receptor modulators, baseline dietary and supplemental calcium and vitamin D intake and history of fracture, no significant association of plasma Lp(a) levels with low hip BMD T-score or hip fracture risk was detected. CONCLUSIONS: These findings suggest that plasma Lp(a) levels are not related to hip BMD T-score or hip fracture events in postmenopausal women. TRIAL REGISTRATION NUMBER: NCT00000611; Post-results.

Effects of alendronate and calcifediol compared to alendronate and cholecalciferol in osteoporotic patients.

BACKGROUND: Several formulations of vitamin D and alendronate are available for the treatment of osteoporosis. The objective of this study was to examine efficacy and safety of calcifediol (25(OH)D) compared to cholecalciferol (vitamin D3) and also the relationship between different formulations of alendronate and adverse reactions. METHODS: We observed a population of women diagnosed with postmenopausal osteoporosis or osteopenia treated with alendronate 70 mg weekly associated to vitamin D3 or 25(OH)D at monthly total dose of 625 µg. Data collected both at baseline (T0) and at follow-up after at least 12 months of therapy (T1) were: demographic characteristics, BMI, full medical history, lumbar T-score, femur T-score, calcium, osteocalcin, alkaline phosphatase, PTH and vitamin D blood level. RESULTS: A total of 362 patients were enrolled in the study. Alendronate 70 mg + calcifediol (A+25(OH)D) group consisted of 202 patients while 160 patients were treated with alendronate 70 mg + cholecalciferol (A+D3). In the A+25(OH)D group, we observed a significant increase in lumbar T-score value (0.26±0.35 vs. 0.13±0.3) and serum vitamin D (20.64±20.71 vs. 6.07±7.61 ng/mL) levels compared to the A+D3 group (P<0.05). The lowest incidence of gastrointestinal adverse reactions was observed among patients taking alendronate 70 mg in drinkable solution form (P<0.05). CONCLUSIONS: Alendronate 70 mg with calcifediol gives a better outcome in the treatment of osteoporosis according to lumbar T-score and vitamin D serum level observed at one-year follow-up compared to alendronate 70 mg with cholecalciferol. Both vitamin D formulations did not show to cause hypercalcemia in this study. Alendronate 70 mg in drinkable solution form is also associated with lowest incidence of gastrointestinal adverse reactions.

Bone protection for early menopausal women in China: standard or half-dose estrogen with progestin? A one-year prospective randomized trail.

The aim of the study is to compare the bone sparing effect of half-dose with standard-dose conjugated equine estrogen (CEE) combined with progestin. A total of 123 participants were administrated with 0.625 mg of CEE and 100 mg of micronized progesterone (MP) in group A, 0.3 mg of CEE and 100 mg of MP in group B, 0.625 mg of CEE and 10 mg of dydrogesterone (DDG) in group C for one year. Percent changes from baseline in BMD at lumbar spine and fracture rate were primary outcomes. Secondary endpoints included changes of BMD at femoral neck, total hip and arm, bone markers (alkaline phosphatase, calcium and phosphorus), serum alanine aminotransferase (ALT) and endometrial thickness. No fractures occurred during the treatment. Standard dose of CEE leads to significant changes in lumbar spine and arm. The 3.78% growth of BMD at femoral neck in group C marked a statistically difference. There was no statistically remarkable bone loss at hip in all three groups. Bone turnover markers and ALT significantly decreased from basic values. Endometrium thickened more with traditional dose of CEE. Both the half and standard dose CEE are effective in BMD preservation among early menopausal women with subtle side effects. Low-dose estrogen is less efficacious than traditional one.

Judgment post-stratification in finite mixture modeling: An example in estimating the prevalence of osteoporosis.

Judgment post-stratification is used to supplement observations taken from finite mixture models with additional easy to obtain rank information and incorporate it in the estimation of model parameters. To do this, sampled units are post-stratified on ranks by randomly selecting comparison sets for each unit from the underlying population and assigning ranks to them using available auxiliary information or judgment ranking. This results in a set of independent order statistics from the underlying model, where the number of units in each rank class is random. We consider cases where one or more rankers with different ranking abilities are used to provide judgment ranks. The judgment ranks are then combined to produce a strength of agreement measure for each observation. This strength measure is implemented in the maximum likelihood estimation of model parameters via a suitable expectation maximization algorithm. Simulation studies are conducted to evaluate the performance of the estimators with or without the extra rank information. Results are applied to bone mineral density data from the third National Health and Nutrition Examination Survey to estimate the prevalence of osteoporosis in adult women aged 50 and over.

Assessing bone quality through mechanical properties in postmenopausal trabecular bone.

BACKGROUND: The inner structure of trabecular bone is a result of structural optimization provided by remodeling processes. Changes in hormonal status related to menopause cause bone tissue loss and micro-architectural deterioration with a consequent susceptibility to fracture. Accumulation of micro-damage in bone, as a function of the rate of production and rate of repair, underlies the development of stress fractures, increasing fragility associated to age and osteoporosis, especially in transmenopausal women. PATIENTS AND METHODS: Quasi-static and nano-dynamic mechanical characterization were undertaken in trabecular bone from femoral neck biopsies of postmenopausal women. AFM (Atomic Force Microscopy) complementary studies were performed to determine nano-roughness (SRa) and the fibrils width of collagen. Nanoindentations were used to quantify transmenopausal changes in intrinsic mechanical properties of trabecular bone: hardness (Hi), modulus of Young (Ei), complex modulus (E*), tan delta (δ), storage modulus (E') and loss modulus (E"). RESULTS: As result of the quasi-static measurements, 0.149 (0.036) GPa and 2.95 (0.73) GPa of Hi and Ei were obtained, respectively. As result of the nano-dynamic measurements, 17.94 (3.15), 0.62 (0.10), 13.79 (3.21 and 6.39 (1.28) GPa of E*, tan (δ), E' and E" were achieved, respectively. 101.07 SRa and 831.28 nm of fibrils width were additionally obtained. CONCLUSIONS: This study poses a first approach to the measurement of bone quality in postmenopausal trabecular bone by combining quasi-static, nano-DMA analysis and tribology of dentin surface through AFM characterization.

The efficacy and safety of herbal medicine BHH10 in postmenopausal women with osteoporosis: study protocol for a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Osteoporosis is becoming more prevalent in aging societies worldwide, and the economic burden attributable to osteoporotic fractures is substantial. The medications presently available to treat osteoporosis have side effects, and the development of safer and more effective treatments is urgently needed. The aim of this study is to evaluate the efficacy and safety of BHH10, a traditional Korean herbal medicine, in the treatment of postmenopausal osteoporosis. METHODS/DESIGN: This is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial and will include 168 postmenopausal women aged 55 years and older with osteoporosis. The participants will be recruited competitively from two sites of the Acupuncture and Moxibustion Department of Kyung Hee University Hospital of Korean Medicine, either Hoegidong or Gangdong in Seoul, Korea. Participants will be assigned randomly to one of two groups, the BHH10 group or the placebo group, in a 1:1 ratio, and will have five scheduled visits. Participants will take two tablets of BHH10 or placebo three times daily for 12 weeks. The primary efficacy outcome is the change in bone mineral density at the lumbar spine (L1-4) between baseline (visit 1) and 12 weeks after randomization (visit 5). Other outcome variables include changes in bone turnover markers, the Deficiency Syndrome of the Kidney Index, EuroQol five-dimension questionnaire score, and laboratory parameters, as well as adverse events. DISCUSSION: To our knowledge, this will be the first clinical trial to assess the efficacy and safety of BHH10 in postmenopausal women with osteoporosis. It is anticipated that the results will contribute to the development of traditional herbal medicines that can be used to treat osteoporosis in postmenopausal women in Korea. If the superiority of BHH10 over placebo is demonstrated, this study could provide the foundation for a phase III clinical trial. The results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Clinical Research Information Service, KCT0001842 . Registered on 14 March 2016.