Increase In Lumbar Spine Bone Mineral Density Research Articles

Teriparatide in postmenopausal osteoporosis: uncovering novel insights into efficacy and safety compared to other treatments - a systematic review and meta-analysis.

The aim of the study was to evaluate the efficacy and safety of teriparatide compared to other treatments for postmenopausal osteoporosis. A review of studies from 2000 to January 2023 analyzed randomized controlled trials on postmenopausal women treated with teriparatide (PTH 1-34), comparing it to placebo or other osteoporosis treatments. The analysis focused on bone mineral density (BMD), bone turnover markers, and clinical outcomes, employing Review Manager 5.4.1 and the RoB 2 tool for bias assessment. Our analysis of 23 randomized controlled trials (RCTs) found that PTH (134) treatment significantly increased lumbar spine BMD (mean difference (MD) = 0.02, 95% CI: 0.01-0.03) and femoral neck BMD (MD = 0.01, 95% CI: 0.00-0.01). However, there were no significant changes in total hip and radial bone BMD among the 3536 and 2046 participants, respectively. We also found that PTH (1-34) increased P1NP in a larger cohort (n = 1415) when compared to osteocalcin (n = 206). Although the risk of adverse events increased (relative risk (RR) = 1.65, 95% CI: 1.32-2.07), the incidence of fractures decreased significantly (RR = 0.57, 95% CI: 0.45-0.072), with no significant difference observed in mortality rates between treatment and control groups. Teriparatide improves lumbar spine and femoral neck BMD in postmenopausal women. Particularly notable is the novel finding regarding its effect on radius BMD, an area less explored in previous research. Despite an uptick in adverse events, the marked decrease in fracture incidence confirms its clinical utility for high-risk osteoporosis patients, highlighting the necessity for ongoing investigations into its full skeletal effects.

A Comprehensive Analysis of Bone Mineral Density Changes across the Lifespan: Insights from National Surveys.

There is limited research providing an overall understanding of bone mineral density (BMD) changes throughout different stages of life. This study aimed to investigate the pattern of BMD changes across childhood, adolescence, adulthood, and old age, as well as exploring the critical time of peak BMD (PBMD). Participants of three major ethnicities from National Health and Nutrition Examination Survey 1999 to 2018 were involved: 46,381 and 20,944 participants aged 8-85 years old were included in the Lumbar spine BMD (LSBMD) and femoral neck BMD (FNBMD) studies, respectively. BMD was measured using dual-energy X-ray absorptiometry. The generalized additive model was used to construct smoothed percentile curves. Both males and females experienced a sharp increase in LSBMD during puberty, with females reaching their PBMD earlier than males. Females' LSBMD remained higher than males' before the age of approximately 50, except for Non-Hispanic Blacks. For males, LSBMD reached a plateau at around 30 years old after reaching the peak value. Females exhibited two peak points on the fitted curves, with the second PBMD occurring around 36-37 years old. Ethnic variations were observed, with Non-Hispanic Blacks displaying the highest BMD levels at all ages. Non-Hispanic Whites and Mexican Americans had lower BMD levels, with Mexican Americans generally exhibiting the lowest BMD. FNBMD reached its peak earlier than LSBMD, and males consistently had higher FNBMD than females. This nationally representative study contributes to the understanding of BMD changes across the lifespan, and might provide guidance for bone health interventions in different population groups.

Lumbar spine densitometry in people with spinal cord injury: Investigation of potential sources of errors

Purpose: People with spinal cord injury (SCI) experience a considerable loss of bone after the injury. Lumbar spine (LS) bone mineral density (BMD) has been reported to be within the normal range, or even higher when assessed with DXA, in people with SCI; hence, it has been hypothesized that sources of error may spuriously increase LS BMD. The aim of this study was to describe the frequency of potential sources of error that may alter LS BMD measurement in a cohort of individuals with chronic SCI at baseline and over a 2-year period. Methods: We analyzed baseline and 2-year follow up DXA scans (Hologic Discovery QDR 4500, Hologic Inc., MA, USA) previously performed from a cohort of males and females with chronic SCI. Two physicians independently reviewed each scan, commented on whether the scan was appropriate for BMD analysis, should be re-analyzed, or be removed from the dataset, and reported on the presence of potential sources of error in LS BMD measurement. Results: We reviewed 115 lumbar spine DXA scans from 58 participants, and 107 (93.0 %) scans from 52 participants presented at least one potential source of error. At baseline, the average number of potential sources of error per scan was 5.5 ± 1.7 and 5.7 ± 1.5 according to rater 1 and rater 2, respectively. Follow-up scans presented an average of 5.6 ± 1.6 and 5.7 ± 1.4 potential sources of error according to rater 1 and rater 2, respectively. Facet sclerosis, osteophytes and difficulty in detecting bone edges were the most prevalent sources of error. Conclusion: The high frequency of potential sources of error is consistent with current recommendations against the use of LS BMD for fracture risk assessment in people with SCI.

Efficacy and safety of romosozumab: a meta-analysis of placebo-controlled trials.

We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis. PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Six trials (7990 patients; follow-up period, 6-12months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12months. Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions).

Clinical spectrum of rare bone fragility disorders and response to bisphosphonate treatment: a retrospective study.

Osteogenesis Imperfecta (OI) is a clinically and genetically heterogeneous group of diseases characterized by brittle bones. Though genetic mutations in COL1A1 and COL1A2 account for approximately 85-90% of OI cases, there are now more than twenty genes described, responsible for rare forms of OI. Treatment is based on the use of bisphosphonates and though it is well established that they increase lumbar spine (LS) bone mineral density (BMD), the clinical impact on fracture reduction is still debated.In this study, we investigated the clinical characteristics of 38 patients with a bone fragility disorder that had variants in non-COL1A1/COL1A2 genes in order to study genotype-phenotype correlations, as the natural history of these rare forms is still not well known. We then studied the usefulness of bisphosphonate treatment by evaluating the effects on LS BMD, annual non-vertebral fracture rate, bone turnover markers and height. This study enabled us to better define the natural history of patients with non-COL1 pathogenic variants. Patients with CRTAP and TMEM38B variants consistently had a prenatal presentation with a short (<3rd p) and bowed femur. Importantly, this prenatal involvement does not predict the postnatal severity of the disease. Regarding treatment by bisphosphonates, all patients showed a significant increase in LS BMD while treated and this increase was dependent on the dose received. The increase in LS BMD also translated in a reduction of fracture rate during treatment. Finally, our study showed that the earlier bisphosphonates are initiated, the greater the fracture rate is reduced.

A novel sequential treatment approach between denosumab and romosozumab in patients with severe osteoporosis.

In patients with severe osteoporosis, the optimal approach for sequential treatment between denosumab and romosozumab has not been established. The ideal strategy would maximise gains in bone mineral density (BMD) with romosozumab and effectively mitigate the risk of rebound increased bone turnover when sequencing from denosumab. Limited studies exploring the sequence from denosumab to romosozumab report only modest-to-no improvement in BMD and inadequate suppression of rebound bone turnover. We describe three patients with severe osteoporosis and multiple fragility fractures despite long-term denosumab. A novel overlapping sequential treatment approach was utilised to maximise therapeutic benefit given these patients had a very high fracture risk. Romosozumab was commenced 3months after the last denosumab dose. Instead of waiting until completion of romosozumab, denosumab was recommenced 6months after commencing romosozumab in response to rising bone turnover markers. Patients experienced a ~ 5-22% increase in lumbar spine BMD, and one patient had an 8% increase in total hip BMD after 12months romosozumab. Serum bone turnover markers demonstrated an anabolic effect of romosozumab occurred despite overlapping treatment with denosumab. Recommencement of denosumab suppressed an increase in bone resorption in all cases. No new vertebral fractures occurred during this treatment. A novel overlapping sequential treatment approach between denosumab and romosozumab produced greater improvements in lumbar spine and hip BMD than previously reported with standard approaches. Larger prospective controlled studies are needed to confirm these findings and establish the optimal use of romosozumab in patients pre-treated with denosumab to maximise BMD gains and minimise fracture risk.

A randomized, double-blind, study to evaluate the efficacy, pharmacodynamics, safety and immunogenicity of FKS518 proposed biosimilar to denosumab with the originator in postmenopausal women with osteoporosis (LUMIADE-3 study).

3155 Background: Biosimilars can increase patient access to treatment. FKS518 is a candidate biosimilar of denosumab, a RANKL inhibitor used in patients with bone metastases from certain solid tumors and in multiple myeloma. To establish biosimilarity, comparative studies are conducted in the most sensitive patient population to detect if there are clinically meaningful differences. LUMIADE-3 was designed to assess the safety and efficacy of FKS518 compared to the originator in postmenopausal women with osteoporosis (PMO). Methods: A randomized, double-blind, multicenter, 2-arm study recruited female patients aged 55 to 85 years with confirmed postmenopausal status and lumbar spine bone mineral density (LS-BMD) T-score ≤ -2.5 and ≥ -4.0, as measured by central dual-energy X-ray absorptiometry (DXA) assessment. Subjects with prior osteoporosis treatment that could add risk for cumulative effect or affect the interpretation of results were excluded. Patients were randomized and received three 60 mg administrations. At week 52, patients receiving denosumab originator were re-randomized to continue their treatment or switch to FKS518 for the third dose. Those receiving FKS518 continued receiving FKS518. The primary efficacy endpoint was the percent change from baseline in LS-BMD DXA at week 52. An analysis of the covariance model was used to compare the two treatments and two separate one-sided tests at alpha=0.05 were performed to assess equivalence. Secondary efficacy endpoints included the percent change from baseline in BMD at the femoral neck and total hip. Results: A total of 553 patients were randomized to FKS518 (n= 276) or the originator (n=277). Clinically relevant increases in LS-BMD were evident at week 52 in both the FKS518 and originator product groups. The results demonstrated therapeutic equivalence: the lower bound of the 90% CI for non-inferiority (-0.05) was above -1.45, and the upper bound of the 90% CI for non-superiority (1.20) was below 1.45. All secondary objectives were met. At week 52, a similar percent change from baseline in BMD at the femoral neck and total hip was observed between the two groups. 374 patients (67.6%) experienced treatment-emergent adverse events: 185 (66.8%) in the FKS518 group and 189 (68.5%) in the originator product group. Safety evaluation did not point to notable differences between FKS518 and the originator product groups. Conclusions: We demonstrated the therapeutic equivalence of FKS518 and originator product. The safety data showed similar safety profiles for the FKS518 and the originator product groups. Results from this study add to the totality of evidence supporting the similarity of FKS518 as a proposed biosimilar to denosumab originator product, a RANKL inhibitor used in patients with bone metastases from solid tumors. Clinical trial information: NCT04934072 .

Risk factors for nonresponse to 2 years of denosumab administration in patients with osteoporosis: A retrospective single-center cohorts study.

To investigate the factors associated with changes in bone mineral density (BMD) and the incidence of fractures in osteoporotic patients treated with denosumab. This retrospective study included 162 osteoporotic patients treated with denosumab for 24 months between 2013 and 2019. Patients were divided according to the changes in BMD as nonresponders (NL group: <3% increase in lumbar spine BMD [LBMD], NH group: <0% increase in femoral neck BMD [FNBMD])or responders (RL group: ≥3% increase in LBMD, RH group: ≥0% increase in FNBMD). The respective changes in the LBMD and FNBMD after 24 months of denosumab treatment were 9.3% (95% confidence interval [CI]: 8.1-10.6) and 3.3% (95% CI: 2.1-4.5). Twenty-eight (17.3%) patients were in the NL group, and 134 (82.7%) were in the RL group. A history of bisphosphonate treatment was a risk factor for being in the NL group (odds ratio [OR]: 3.84, 95% CI: 1.38-10.71, p = 0.007; adjusted OR: 3.21, 95% CI: 1.01-10.19, p = 0.048). Although the NH (n = 48; 30.8%) and RH (n = 108; 69.2%) groups had similar baseline characteristics, the NH group had a significantly higher baseline FNBMD than the RH group (p = 0.003). The change in FNBMD was negatively associated with the FNBMD at baseline (r = -0.34, p < 0.001). No new osteoporotic fractures occurred in either group during follow-up. In osteoporotic patients receiving denosumab treatment, a history of bisphosphonate treatment was a risk factor for a lack of increase in LBMD, and a higher FNBMD at baseline was negatively associated with the change in FNBMD.

Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study.

Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP). We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2years) or continuing ongoing denosumab alone (>2years). We collected serum samples for bone turnover markers, bone modulators, and calcium phosphate metabolism at baseline, month 3 and month 6. BMD was assessed at baseline and after 6months. Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab, and 22 continued denosumab alone. BMD increased significantly at all sites at 6months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8%, and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and +99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups, and Dkk1 did not change. Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD vs denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.

FRI683 Every Dose Counts: Response To Half The Recommended Dose Of Romosozumab

Abstract Disclosure: B.P. Ramchandani: None. F.S. Mirza: None. Introduction: Romosozumab (RSB) is a monoclonal antibody that inhibits sclerostin, increases bone formation and decreases bone resorption. It was approved by FDA in 2019 at a dose of 210 mg monthly for 1 year, followed by an anti-resorptive medication. We present a case of a 76 y.o. female with severe osteoporosis and history of intolerance to multiple medications, who was given half the monthly recommended dose of Romo due to extreme concern about side effects. We hereby report the response of her bone density to the treatment. Case Description: A 76-year-old female with history of primary biliary cirrhosis, Sjogren’s syndrome, hemorrhagic duodenal ulcer, s/p subtotal gastrectomy in 1962 presented for evaluation of severe osteoporosis. Fracture history was significant for T11 compression fracture in 2020 requiring kyphoplasty, and a T10 inferior endplate compression fracture requiring vertebroplasty in 2022. Osteoporosis was first diagnosed in 2005. She was intolerant of teriparatide in 2005 (stopped after six months due to nausea, hypercalcemia, cramps, pain in extremities and fatigue). Zoledronic acid (ZA) was administered in 2006 and 2008. Baseline urine telopeptide cross-links (NTx) was low at 18 which decreased to 10 while on ZA and further infusions were held. She declined denosumab and teriparatide was tried again in 2013 that she did not tolerate. She received ZA again in 2016. BMD did not improve on ZA and she declined further infusions. She was physically active and walked daily and was taking calcium citrate, vitamin D and ursodiol during this time. On examination, she was frail and elderly, with BMI of 16.6 mg/kg2. She had mild kyphoscoliosis of the spine with no spinal or paraspinal tenderness. Remainder of the exam was unremarkable. Laboratory evaluation showed normal serum calcium (9.5 mg/dl), albumin (4.1g/dl), Vit D 25-OH (36 mg/ml), bone specific alkaline phosphatase of 22.7 U/L and urine NTx of 23 nm BCE/mm creatinine. Bone density (BMD) in January 2022 showed lumbar spine (LS) BMD of 0.613 g/cm2 (T-score −4.7) and a total hip BMD of 0.575 g/cm2 (T-score −3.4). She was reluctant to consider any medications due to concern about side effects, but finally agreed to a trial of RSB at half the recommended dose at 105 mg monthly for 12 months. DXA scan a year later showed 17% increase in LS BMD (0.715 g/cm2, T-score -3.9), with stable total hip BMD. She has been transitioned to denosumab, which she was now agreeable to take. Discussion: Our patient showed significant improvement in BMD with half the recommended dose of RSB, comparable to the increase in LS BMD reported in phase 3 trials. She was petite and her weight-based dose was just short of 3 mg/kg body weight. Phase 1 and 2 studies had tried weight based and smaller doses of Romo and showed improvement in BMD. This case highlights the need for additional studies with weight-based dosing of RSB, which may reduce the cost of treatment. Presentation: Friday, June 16, 2023

Comparative Effectiveness of Therapeutic Interventions in Pregnancy and Lactation-Associated Osteoporosis: A Systematic Review and Meta-analysis.

The optimal management of pregnancy and lactation-associated osteoporosis (PLO) has not been designated. To systematically review the best available evidence regarding the effect of different therapeutic interventions on bone mineral density (BMD) and risk of fractures in these patients. A comprehensive search was conducted in PubMed/Scopus databases until December 20, 2022. Data were expressed as weighted mean difference (WMD) with 95% CI. The I2 index was employed for heterogeneity. Studies conducted in women with PLO who received any antiosteoporosis therapy were included. Studies including women with secondary causes of osteoporosis or with transient osteoporosis of the hip were excluded. Data extraction was independently completed by 2 researchers. Sixty-six studies were included in the qualitative analysis (n = 451 [follow-up time range 6-264 months; age range 19-42 years]). The increase in lumbar spine (LS) BMD with calcium/vitamin D (CaD), bisphosphonates, and teriparatide was 2.0% to 7.5%, 5.0% to 41.5%, and 8.0% to 24.4% at 12 months, and 11.0% to 12.2%, 10.2% to 171.9%, and 24.1% to 32.9% at 24 months, respectively. Femoral neck (FN) BMD increased by 6.1% with CaD, and by 0.7% to 18% and 8.4% to 18.6% with bisphosphonates and teriparatide (18-24 months), respectively. Meta-analysis was performed for 2 interventional studies only. Teriparatide induced a greater increase in LS and FN BMD than CaD (WMD 11.5%, 95% CI 4.9-18.0%, I2 50.9%, and 5.4%, 95% CI 1.2-9.6%, I2 8.1%, respectively). Due to high heterogeneity and lack of robust comparative data, no safe conclusions can be made regarding the optimal therapeutic intervention in women with PLO.

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.

Efficacy and safety of medications for osteoporosis in kidney transplant recipients or patients with chronic kidney disease: A meta-analysis.

This study conducted a meta-analysis to analyze the efficacy and safety of osteoporosis medications in kidney transplant recipients and patients with chronic kidney disease (CKD). PubMed, Embase, the Cochrane Central Register of Controlled Trials were searched from the date of their inception through October 21, 2022. We performed a meta-analysis of the efficacy and safety of osteoporosis medications in adult patients with stage 3-5 CKD or kidney transplant recipients enrolled in randomized clinical trials (RCTs). We calculated the standard mean deviations with 95% confidence intervals (CI) for bone mineral density (BMD) and T scores after 6 and 12 months treatment, pooled odds ratio and 95% CI for fracture risk, and summarized adverse events. The inclusion criteria were met by 27 studies. Out of this, 19 studies were included for the meta-analysis. In stage 3-4 CKD patients, alendronate increased lumbar spine BMD. In patients at stage 5 CKD and undergoing hemodialysis, alendronate and raloxifene increased lumbar spine BMD. After 6 months, the BMD of kidney transplant recipients was seen to be significantly increased; however, there was no difference after 12 months, and the risk of fracture did not reduce. Thus, there is no evidence that these medications reduce the risk of fracture, and their effect on BMD and fracture remains unproven. These medications may increase the incidence of adverse events and their safety needs to be further evaluated. Therefore, we cannot draw a definitive conclusion about the efficacy and safety of osteoporosis medications in the above group of patients.

The effect of virtual reality technology on anti-fall ability and bone mineral density of the elderly with osteoporosis in an elderly care institution

ObjectiveTo explore the impact of virtual reality (VR) training on anti-fall ability and bone mineral density (BMD) among elderly patients admitted to a healthcare institution.MethodsPeople (aged 50) with osteoporosis in an elderly care institution in Anhui Province June 2020 to October 2021 were selected and randomly divided into VR group (n = 25) and control group (n = 25). In VR group, the virtual reality rehabilitation training system was used for training, while control group was treated with traditional fall prevention exercise intervention. The changes of Berg Balance Scale (BBS), timed up and go test (TUGT), functional gait assessment (FGA), bone mineral density (BMD) and falls during 12 months of training were compared between the two groups.ResultsBBS and FGA were positively correlated with BMD of the lumbar vertebrae and femoral neck, and TUGT was negatively correlated with BMD of the lumbar vertebrae and femoral neck. After 12 months of training, the BBS score, TUGT evaluation and FGA evaluation of the two groups were significantly improved compared with those prior to training (P < 0.05). However, there was no significant difference in the lumbar spine and femoral neck BMD between the two groups 6 months after the intervention. The femoral neck and lumbar spine BMD of the VR group improved, and it was significantly higher than that of the control group 12 months after the intervention. Nevertheless, there was no significant difference in terms of the incidence of adverse events between the two groups.ConclusionVR training can improve anti-fall ability and increase femoral neck and lumbar spine BMD and can effectively prevent and reduce the risk of injury among elderly people with osteoporosis.

Association of hormone preparations with bone mineral density, osteopenia, and osteoporosis in postmenopausal women: data from National Health and Nutrition Examination Survey 1999-2018.

This study aimed to evaluate the associations of hormone preparations with lumbar spine bone mineral density (BMD), osteopenia, and osteoporosis in postmenopausal women, and whether these impacts persisted after hormone preparations were discontinued. A total of 6,031 postmenopausal women were enrolled and divided into seven groups based on the types of hormone preparations. Among them, 1,996 participants were further divided into a current users (CU) group and a past users (PU) group. Multivariable linear regression models or logistic regression models were used to evaluate the associations of hormone preparation with lumbar spine BMD, osteopenia, and osteoporosis. Combined oral contraceptive pills, estrogen-only pills, estrogen/progestin combo pills, estrogen-only patches, or the use of more than two kinds of hormone preparations were positively associated with lumbar spine BMD (all P < 0.05). Except for estrogen-only patches, other hormone preparations also had a protective effect against osteopenia (all OR < 1, all P < 0.05), but none of them were associated with osteoporosis prevalence (all P > 0.05). The BMD increased by 0.10 and 0.04 g/cm 2 in the CU and PU groups, respectively, compared with the nonusers group (all P < 0.05). In both the CU and PU groups, the risk of osteopenia was reduced (OR, 0.34 and 0.57, respectively). Hormone preparations increase lumbar spine BMD in postmenopausal women and exert a protective effect against osteopenia. These impacts persisted after hormone preparations were discontinued. Hormone preparations, however, were not associated with osteoporosis prevalence.

The Clinical Effectiveness of Denosumab (Prolia®) for the Treatment of Osteoporosis in Postmenopausal Women, Compared to Bisphosphonates, Selective Estrogen Receptor Modulators (SERM), and Placebo: A Systematic Review and Network Meta-Analysis.

To assess the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen receptor modulators (SERMs; bazedoxifene, raloxifene) or placebo, for the treatment of osteoporosis in postmenopausal women (PMW). Systematic searches were run in PubMed, Embase & Cochrane Library on 27-April-2022. Randomized controlled trials (RCTs) that included osteoporotic PMW allocated to denosumab, SERMs, bisphosphonates, or placebo were eligible for inclusion. RCTs were appraised using Cochrane Risk of Bias 2.0. Bayesian network and/or pairwise meta-analyses were conducted on predetermined outcomes (i.e. vertebral/nonvertebral fractures, bone mineral density [BMD], mortality, adverse events [AEs], serious AEs (SAEs), withdrawals due to AEs, AEs caused by denosumab discontinuation). A total of 12 RCTs (k = 22 publications; n = 25,879 participants) were included in the analyses. Denosumab, reported a statistically significant increase in lumbar spine (LS) and total hip (TH) BMD, compared to placebo. Similarly, denosumab also resulted in a statistically significant increase in TH BMD compared to the raloxifene and bazedoxifene. However, relative to denosumab, alendronate, ibandronate and risedronate resulted in significant improvements in both femoral neck (FN) and LS BMD. With regards to vertebral fractures and all safety outcomes, there were no statistically significant differences between denosumab and any of the comparator. Relative to placebo, denosumab was associated with significant benefits in both LS and TH BMD. Additionally, denosumab (compared to placebo) was not associated with reductions in vertebral and nonvertebral fractures. Finally, denosumab was not associated with improvement in safety outcomes, compared to placebo. These findings should be interpreted with caution as some analyses suffered from statistical imprecision.

Synergistic Effects of Combined Concurrent Training and Eri-Polyunsaturated Fatty Acid Supplementation on Bone Mineral Density, Muscle Strength, and Inflammation.

Obesity has been associated with lower bone mineral density (BMD) and rapid muscle weakness. Regular exercise and polyunsaturated fatty acid (PUFA) consumption have been recognized as nonpharmaceutical approaches to increase BMD and ameliorate muscle weakness. This study aimed to determine the effects of concurrent training (CCT) and Eri-PUFA supplementation on BMD, muscular strength, and inflammation in obese adults. A total of 33 obese participants were randomly assigned to one of three groups (n=11 per group): (1) a placebo group; (2) an Eri-PUFA ingestion group (ERI); or (3) a CCT and Eri-PUFA ingestion group (CCT+ERI). The ERI and CCT+ERI groups received approximately 2.5 g of linolenic acid per day from Eri silkworm pupae. The exercise program included aerobic and resistance exercises performed under supervision three times per week for 8 weeks. Before and after the 8-week intervention, BMD, muscular strength, and inflammatory markers were measured. Only the CCT+ERI group showed a significant increase in lumbar spine BMD (5.1%, P<0.01) and upper-body muscle strength (16.9%, P<0.01) after the intervention, with differences between the groups. After the intervention, both the ERI and CCT+ERI groups showed a significant decrease in the monocyte-to-lymphocyte ratio (-25%, P<0.01 and -21.4%, P<0.05, respectively) and tumor necrosis factor-alpha (-21.6%, P<0.05 and -19.4%, P<0.05, respectively). These findings demonstrate that combining CCT and Eri-PUFA supplementation increases BMD and upper-body muscular strength and decreases inflammation. Although Eri-PUFA consumption did not affect BMD or muscle strength directly, it may have an additive effect on BMD by reducing inflammation.

Effect of Teriparatide on Bone Mineral Density and Bone Markers in Real-Life: Argentine Experience.

To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone markers under clinical practice conditions. To assess whether the results in real-life match those published in clinical trials. Cross-sectional study of postmenopausal women treated with TPTD for at least 12 months. 264 patients were included in the study. Main characteristics are as follows: age: 68.7 ± 10.2 years, previous fractures: 57.6%, and previously treated with antiresorptive (AR-prior): 79%. All bone turnover markers studied significantly increased after 6 months. CTX and BGP remained high up to 24 months, but total and bone alkaline phosphatase returned to basal values at month 18. There was a significant increase in lumbar spine (LS) BMD after 6 months (+6.2%), with a maximum peak at 24 months (+13%). Femoral neck (FN) and total hip (TH) BMD showed a significant increase later than LS (just at month 12), reaching a maximum peak at month 24 (FN + 7.9% and TH + 5.5%). A significant increase in LS BMD was found from month 6 to month 24 compared to basal in both AR-naïve, and AR-prior patients (+16.7% and +10.5%, respectively), without significant differences between the two groups. Comparable results were found in FN and TH BMD. Main conclusions. As reported in real-life clinical studies, treatment of osteoporotic postmenopausal women with TPTD induced a significant increase in bone turnover markers from month 6 onward and an increase in BMD from months 6-12 with continuous gain up to month 24. The real-life results of our study matched the results of randomized clinical trials. In addition, TPTD induced an increase in BMD, regardless of the previous use of AR.

Effect of Zoledronic Acid in Hepatic Osteodystrophy: A Double-Blinded Placebo-Controlled Trial.

Literature on the treatment of pre-transplant hepatic osteodystrophy (HOD) is limited. The general treatment measures and their timing are currently adopted from the literature on postmenopausal osteoporosis. Therefore, we conducted this randomized study to investigate the effect of zoledronic acid (ZA) on HOD. We randomized 36 male patients with cirrhosis (Child-Pugh class A and B) into 19 to the ZA arm and 17 to the placebo arm, respectively. Patients in the ZA arm received a single infusion of 4 mg ZA dissolved in 100 mL of normal saline at baseline, while patients in the placebo arm received a similar infusion of normal saline at baseline. The primary outcome of the study was the change in lumbar spine bone mineral density (LS-BMD) at 12 months. Of 36 patients, 28 completed the study (15 in the ZA arm and 13 in the placebo arm). The mean increase in LS-BMD (g/cm2) in the ZA and placebo arms was 5.11% (3.50) and 0.72% (4.63) [P = 0.008], respectively. The trabecular bone score (TBS) did not improve significantly in either arm. The incidence of vertebral fractures (VFs) was similar in both arms. There was a significant decrease in plasma beta-C-terminal telopeptide (β-CTX) levels in the ZA arm compared to the placebo arm, while the change in plasma levels of procollagen 1 intact N-terminal propeptide (P1NP) was similar in both arms. Six patients (31.6%) in the ZA arm experienced adverse reactions such as fever and myalgia. ZA improved LS-BMD in male patients with HOD by decreasing bone resorption. However, it may not improve trabecular microarchitecture or prevent morphometric VFs in this population.

Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: A randomized, double-blind, placebo-controlled, multicenter phase III study.

This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50-85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60​mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Of the 448 randomized patients, 409 (LY06006, n​=​311; placebo, n​=​98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P​<​0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1​N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs. In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies. In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.