Change In Spine Bone Mineral Density Research Articles

Assessing Change in Spine Bone Density from Different Numbers and Combinations of Lumbar Vertebrae: The Manitoba BMD Registry

Introduction: Change in bone mineral density (BMD) is considered significant when it exceeds the 95 % least significant change (LSC) derived from that facility's precision study. The lumbar spine is often affected by structural artifact such that not all four lumbar vertebrae are evaluable. Guidelines suggest using a site-matched LSC when omitting vertebrae from the BMD measurement. The current study describes significant BMD change related to intervening anti-osteoporosis treatment for different numbers and combinations of lumbar vertebrae using site-matched LSC values.Methodology: We identified 10,526 untreated adult women mean age 59.6 years with baseline and repeat spine BMD testing (mean interval 4.7 years) where all 4 lumbar vertebrae were evaluable. Change in spine BMD for different combinations of lumbar vertebrae was assessed in relation to intervening anti-resorptive treatment, contrasting women with high treatment exposure (medication possession ratio, MPR ≥ 0.8) versus women who remained untreated. Site-matched LSC values were derived from 879 test-retest precision measurements.Results: There was consistent linear trend between increasing MPR and BMD change exceeding the LSC for all lumbar vertebral combinations, positive with BMD increase and negative with BMD decrease (all p-trend <0.001). In the high treatment exposure group, mean percent increases in spine BMD were similar for all vertebral combinations, from L1-4 to a single vertebra. In untreated women, mean percent decreases in spine BMD were also similar for all vertebral combinations. The net treatment response (proportion of women with treatment-concordant changes minus proportion with treatment-discordant changes exceeding the LSC) was 29.7 % for 4 vertebrae, 27.5-30.0 % for 3 vertebrae, 22.4-28.5 % for 2 vertebrae, and 18.1-21.9 % for a single vertebra.Conclusions: All numbers and combinations of lumbar vertebrae, when used in conjunction with site-matched LSC values, can provide clinically meaningful follow-up in treated and untreated patients, even when spine BMD is based on a single vertebral body.

Bone mineral density fall during aromatase inhibitor treatment may predict lower breast cancer recurrence.

Aromatase inhibitors (AIs) are associated with reduction in bone mineral density (BMD). The use of bone strengthening agents zoledronic acid and denosumab are associated with improved breast cancer outcomes for post-menopausal patients treated with AIs. This study investigates whether change in BMD with AI therapy is associated with breast cancer recurrence. A cohort of patients treated at a single institution diagnosed with hormone receptor-positive breast cancer with baseline BMD and subsequent BMD test while receiving adjuvant aromatase inhibitor therapy were studied. Demographic, treatment and outcome data was obtained. Simple and multiple linear regression analysis was performed to investigate predictors of annual percent BMD change at the LS and hip. Univariate and multivariate Cox proportional hazards modelling were undertaken to investigate predictors of breast cancer recurrence. 353 patients eligible patients were identified. In multivariate analysis of lumbar spine BMD change, the difference between those in quartile 1, which showed the greatest reduction in BMD, and quartile 3, with substantially less reduction, was significant (HR = 3.02, 95% CI 1.15-7.90 p = 0.025). Hip BMD reduction was also not significantly associated with breast cancer recurrence. The two quartiles with the least reduction in hip BMD showing a non-significant reduced risk of recurrence relative to the quartile with the greatest (p = 0.10). The findings suggest an association may exist between lumbar spine BMD change and breast cancer recurrence for patients treated with adjuvant AI. Further research is required to determine whether BMD change can be utilised as a biomarker.

Delayed versus immediate use of zoledronic acid for postmenopausal patients with ER/PR positive early breast cancer who are using adjuvant letrozole.

8 Background: Aromatase inhibitors are the standard adjuvant therapy for postmenopausal women with hormone receptor (HR) positive early breast cancer (EBC). In such patients, a significant reduction in bone density was observed. To stop bone loss, bisphosphonates have a powerful effect on reducing bone resorption and improving the survival of patients with EBC. This study compared potential bone-protection of immediate versus delayed administration of zoledronic acid (ZOL) in patients with EBC receiving adjuvant letrozole. Methods: In a prospective two-arm comparative study, 65 postmenopausal patients with HR+ EBC in whom adjuvant letrozole treatment was initiated (2.5 mg/day for 5 years), we included either (45) immediate ZOL treatment or (20) delayed ZOL treatment (both at 4 mg every 6 months). Patients in the delayed ZOL group received ZOL only for fracture or increased bone pain or developed bone mineral density (BMD)T score = or &lt; -2.0. We aimed to assess the change in lumber spine BMD every 3 months for 24 months for both immediate and delayed arm patients, in addition to evaluating bone pain deterioration and the disease-free survival (DFS). Results: Analysis of data showed significant differences between immediate and delayed arms in the first three BMD measurements with mean values were -1.55± 0.4 vs. -1.9± 0.2, -1.56± 0.3 vs. -2.5± 0.3, and -1.4±0.3 vs. -3.5± 0.3 with p&lt;0.002, 0.001, 0.0001 respectively. Despite ZOL administration in delayed arm patients was initiated 6 months later than immediate arm patients, improvement of BMD was detected in delayed arm later on. The median DFS for immediate and delayed arms were 39± 0.6 months and 21± 0.4 months respectively with p&lt;0.001 in both. Although, in pre-ZOL bone pain scoring, most patients of delayed arm (75%) were found to have a score of 3 compared to 51.1% of immediate arm, significant improvement in bone pain scores in both arms separately after ZOL administration was noted with p-values 0.031, and 0.025 respectively. Conclusions: Immediate ZOL administration prevented bone loss, improved bone pain, and ameliorate DFS in postmenopausal women with HR+ EBC receiving adjuvant letrozole. Clinical trial information: PACTR202112813934276.

Bone mineral density response to antiosteoporotic drugs in older depressed adults.

This study aimed to evaluate the effects of depression and antidepressants on bone mineral density (BMD) and response to antiosteoporotic agents in older adults. A total of 198 participants with osteoporosis, aged 65 and over, were included in this retrospective study. BMD was measured by dual-energy x-ray absorptiometry scanning at baseline and month 24. Eighty-three of the 198 patients had a diagnosis of depression, and all were serotonergic antidepressant users. Baseline BMD was similar in depressed and non-depressed patients. Lumbar spine BMD change was significantly lower in depressed patients than non-depressed patients (2.89% and 4.85%, respectively, p < 0.001). In addition, of those receiving denosumab treatment, depressed ones had lower lumbar spine BMD changes. Depression and/or antidepressant use was an independent variable for non-response to osteoporosis treatment in both the femoral neck (p = 0.008, OR = 2.61) and lumbar spine (p = 0.015, OR = 6.87), while alendronate and zoledronic acid were independent variables for non-response in the femoral neck and total femur compared to denosumab. Our study has shown that the presence of depression and/or serotonergic antidepressant use was associated with non-response to osteoporosis treatment in older adults. The results of our study may guide physicians to make treatment decisions in older individuals with depression.

Bisphosphonates Alleviate Bone Loss in People with Acute Spinal Cord Injury：A Systematic Review and Meta-Analysis

Bone loss is not to be underestimated in people with acute spinal cord injury (SCI). Bisphosphonates can inhibit the bone resorption of osteoclast. To study whether the early application of bisphosphonates can alleviate bone loss after acute SCI, we included 7 randomized controlled trials for meta-analysis. Seven randomized controlled trials were found in literature databases. The percentage change in bone mineral density (BMD) at different sites were primary outcomes and serum bone turnover markers were secondary outcomes. A random-effects model was selected for meta-analysis. There were significant differences in the percentage change in BMD of the lumbar spine, total hip, and femoral neck between the bisphosphonates and control groups, but not in the percentage change in distal femur BMD. Besides, there were no statistically significant differences between the groups in the bone formation marker Procollagen type 1N propeptide; bisphosphonates were effective in reducing the C-terminal telopeptide at the 6-month follow-up, but not at the 12-month follow-up. Subgroup analysis of the effects of zoledronate showed positive effects on BMD of the lumbar spine, total hip, and femoral neck at the 6-month follow-up and showed positive effects on BMD of the total hip and femoral neck at the 12-month follow-up. Bisphosphonates can effectively alleviate the bone loss of the lumbar spine, total hip, and femoral neck in patients with acute SCI, and early application is advocated.

Effect of 24-Week, Late-Evening Ingestion of a Calcium-Fortified, Milk-Based Protein Matrix on Biomarkers of Bone Metabolism and Site-Specific Bone Mineral Density in Postmenopausal Women with Osteopenia.

Dietary calcium intake is a modifiable, lifestyle factor that can affect bone health and the risk of fracture. The diurnal rhythm of bone remodelling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of daily, bed-time ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or control (CON), for 24 weeks, on serum biomarkers of bone resorption (C-terminal telopeptide of type I collagen, CTX) and formation (serum pro-collagen type 1 N-terminal propeptide, P1NP), and site-specific aerial bone mineral density (BMD), trabecular bone score (TBS), in postmenopausal women with osteopenia. The MBPM supplement increased mean daily energy, protein, and calcium intake, by 11, 30, and 107%, respectively. 24-week supplementation with MBPM decreased CTX by 23%, from 0.547 (0.107) to 0.416 (0.087) ng/mL (p < 0.001) and P1NP by 17%, from 60.6 (9.1) to 49.7 (7.2) μg/L (p < 0.001). Compared to CON, MBPM induced a significantly greater reduction in serum CTX (mean (CI95%); −9 (8.6) vs. −23 (8.5)%, p = 0.025 but not P1NP −19 (8.8) vs. −17 (5.2)%, p = 0.802). No significant change in TBS, AP spine or dual femur aerial BMD was observed for CON or MBPM. This study demonstrates the potential benefit of bed-time ingestion of a calcium-fortified, milk-based protein matrix on homeostatic bone remodelling but no resultant treatment effect on site-specific BMD in postmenopausal women with osteopenia.

Effects of Bisphosphonates Treatments in Osteopenic Older Women: A Systematic Review and Meta-Analysis

Aims: To review the effects of bisphosphonates on bone density, fractures, and bone markers in osteopenic older women. Methods: Relevant articles published before February 2022 were searched in PubMed, EMBASE, and the Cochrane Library. All randomized controlled trials that reported incident fractures, bone mineral density (BMD), bone markers, or adverse events with bisphosphonates in osteopenic older women were included. The quality of included studies was assessed using the Cochrane Risk of Bias tool. The risk ratios (RRs) for fractures, net percent change in bone mineral density and differences in bone markers were calculated using a meta-analysis. Results: A total of 11 studies were included in our meta-analysis. Bisphosphonates significantly increased the percent changes in the lumbar spine BMD (WMD, 5.60; 95% CI, 4.16–7.03; I 2 = 93.6%), hip BMD (WMD, 4.80; 95% CI, 2.93 to 6.66; I 2 = 97.1%), total body BMD (WMD, 3.24; 95% CI, 2.12–4.35; I 2 = 90.9%), femoral neck BMD (WMD, 4.02; 95% CI, 1.70–6.35; I 2 = 91.8%) and trochanter BMD (WMD, 5.22; 95% CI, 3.51–6.93; I 2 = 83.6%) when compared to placebo. Zoledronate was associated with a great treatment effect on fragility fracture (RR, 0.63; 95% CI, 0.50–0.79), clinical vertebral fracture (RR, 0.41; 95% CI, 0.22–0.76), and radiographic vertebral fracture (RR, 0.60; 95% CI, 0.27–1.35) compared to placebo. Meanwhile, alendronate was also associated with beneficial effects on fragility fracture (RR, 0.40; 95% CI, 0.15–1.07), clinical vertebral fracture (RR, 0.46; 95% CI, 0.17–1.24), and radiographic vertebral fracture (RR, 0.64; 95% CI, 0.38–1.09). In addition, the use of bisphosphonates reduced the concentration of procollagen type I N-terminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX) over placebo by 15.79 (95% CI, −18.92 to −12.66; I 2 = 28.4%), −0.23 (95% CI, −0.35 to −0.10; I 2 = 91.3%), respectively. Although there was insufficient evidence to determine their safety, these bisphosphonates may have an effect on cancer, cardiac events, and mortality in osteopenic older women. Conclusion: All bisphosphonates examined were associated with beneficial effects on fractures, BMD, and bone markers in women with osteopenia. Further randomized controlled trials are necessary to clarify the safety of bisphosphonates in women with osteopenia.

Simplification from tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted protease inhibitor to ritonavir-boosted atazanavir plus lamivudine in virologically suppressed HIV-infected adults with osteopenia: a pilot study.

Tenofovir disoproxil fumarate, particularly when given with a ritonavir-boosted PI, reduces bone mineral density (BMD) and increases bone turnover markers (BTMs). Ritonavir-boosted atazanavir plus lamivudine is a feasible simplified option. We evaluated whether switching from a triple ritonavir-boosted PI plus tenofovir disoproxil fumarate to a two-drug regimen of lamivudine plus ritonavir-boosted atazanavir would improve BMD. Single-arm pilot study. Virologically suppressed patients on tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted PI with low BMD, without previous resistance mutations and/or virological failure to study drugs were switched to 100/300 mg of ritonavir-boosted atazanavir plus 300 mg of lamivudine once daily. The primary endpoint was BMD change by DXA at Week 48. There were 31 patients, 4 (13%) female, and median age was 40 years. Seven participants (22.5%) had osteoporosis. At 48 weeks, mean (SD) changes in spine and hip BMD were +0.01 (0.03) (P = 0.0239) and +0.013 (0.03) g/cm2 (P = 0.0046), respectively. Mean (SD) T-score changes were +0.1 (0.23) (P = 0.0089) and +0.25 (0.76) (P = 0.0197), respectively. N-telopeptide and urine tenofovir disoproxil fumarate toxicity markers showed significant improvements. One participant withdrew from the study and two were lost to follow-up. There were no virological failures, or serious or grade 3-4 adverse events. Switching from a tenofovir disoproxil fumarate plus ritonavir-boosted PI triple therapy to a lamivudine plus ritonavir-boosted atazanavir two-drug regimen in virologically suppressed HIV-infected adults with low BMD was safe, increased low BMD and reduced plasma markers of bone turnover and urine markers of tenofovir disoproxil fumarate toxicity over 48 weeks.

Pharmacogenetics of Osteoporosis: A Pathway Analysis of the Genetic Influence on the Effects of Antiresorptive Drugs.

Osteoporosis is a skeletal disorder defined by a decreased bone mineral density (BMD) and an increased susceptibility to fractures. Bisphosphonates and selective oestrogen receptor modulators (SERM) are among the most widely used drugs. They inhibit bone resorption by targeting the mevalonate and oestrogen pathways, respectively. The aim of this study was to determine if common variants of genes in those pathways influence drug responses. We studied 192 women treated with oral aminobisphosphonates and 51 with SERMs. Genotypes at 154 SNPs of the mevalonate pathway and 806 in the oestrogen pathway were analyzed. Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. After multivariate analyses, genotypes combining genes FDPS and FNTA showed a stronger association with bisphosphonate response (r = 0.34; p = 0.00009), whereas the combination of CYP19A1 and PDSS1 genotypes was associated with the response to SERMs (r = 0.62, p = 0.0003). These results suggest that genotyping genes in these pathways may help predict the response to antiresorptive drugs and hence make personalized therapeutic choices.

Raloxifene Use After Denosumab Discontinuation Partially Attenuates Bone Loss in the Lumbar Spine in Postmenopausal Osteoporosis.

Discontinuation of denosumab (DMab) is associated with decline in bone density. Whether raloxifene can be effective to attenuate bone loss after DMab discontinuation in certain conditions when other antiresorptives cannot be used remains unclear. Data on postmenopausal women with osteoporosis who discontinued DMab treatment after short-term use (1-to-4 doses) at Severance Hospital, Seoul, Korea, between 2017 and 2021 were reviewed. Changes in bone mineral density (BMD) at 12months after DMab discontinuation was compared between sequential raloxifene users (DR) and those without any sequential antiresorptive (DD) after 1:1 propensity score matching. In matched cohort (66 patients; DR n = 33 vs. DD n = 33), mean age (69.3 ± 8.2years) and T-score (lumbar spine - 2.2 ± 0.7; total hip - 1.6 ± 0.6) did not differ between two groups at the time of DMab discontinuation. Sequential treatment to raloxifene in DR group attenuated the bone loss in lumbar spine after DMab discontinuation compared to DD group (DR vs. DD; - 2.8% vs. - 5.8%, p = 0.013). The effect of raloxifene on lumbar spine BMD changes remained robust (adjusted β + 2.92 vs. DD, p = 0.009) after adjustment for covariates. BMD loss at femoral neck (- 1.70% vs. - 2.77%, p = 0.673) and total hip (- 1.42% vs. - 1.44%, p = 0.992) did not differ between two groups. Compared to BMD at DMab initiation, DR partially retained BMD gain by DMab treatment in lumbar spine (+ 3.7%, p = 0.003) and femoral neck (+ 2.8%, p = 0.010), whereas DD did not. Raloxifene use after DMab treatment attenuated lumbar spine BMD loss in postmenopausal women with short exposures (< 2years) to DMab.

Bone mass measurement by DXA should be interpreted with caution in the CKD population with vascular calcification

BackgroundKDIGO guidelines suggest the use of dual-energy X-ray absorptiometry (DXA) to assess bone mineral density (BMD) in patients with CKD 3a-5D. Previous studies have demonstrated an association between trabecular bone mass loss and coronary artery calcification (CAC) progression. This study aimed to prospectively investigate the relationship between BMD changes, quantified by DXA, and CAC progression in the non-dialyzed CKD population. MethodsIn this post hoc study, BMD by DXA was measured at the lumbar spine and total hip at baseline and 12-months. Patients were categorized according to BMD changes into 3 different groups: LOSS, UNCHANGED and GAIN. CAC quantification was obtained by multislice computed tomography at baseline and 12-months. Results87 patients (55.6 ± 10.7 years, 62% males, 30% diabetic, eGFR = 39.2 ± 18.1 mL/min/1.73m2) were enrolled. CAC was found in 41 (47%) of the patients at baseline and CAC progression in 25 (64%) of them. Considering the lumbar spine and total hip BMD changes together, 24%, 48%, and 25% of the patients were in the LOSS, UNCHANGED and GAIN groups, respectively. Compared to the UNCHANGED or LOSS groups, the GAIN group had an increase in calcium score (p = 0.04) and a higher proportion of patients with CAC progression (p = 0.01). In the logistic regression analysis, CAC progression was 4.5 times more likely to be in the GAIN group. ConclusionsThe association between the increase in BMD values and the progression of vascular calcification was the result of two concomitant processes overlapping, leading to a misinterpretation of DXA results. Thus, the use of DXA for the evaluation of bone mass, especially at the lumbar spine, must be applied with restraint and its results very carefully interpreted in CKD patients.

A model-based analysis to guide gonadotropin-releasing hormone receptor antagonist use for management of endometriosis.

AimsTo identify linzagolix doses, an oral GnRH receptor antagonist, that effectively lower oestradiol (E2) to relieve endometriosis‐related pelvic pain without compromising bone health.MethodsIntegrated statistical, pharmacokinetic–pharmacodynamic and systems pharmacology models were developed from Phase 1 and 2 clinical trial data in healthy volunteers and patients, receiving linzagolix 25–200 mg daily or placebo, and analysed simultaneously. The main outcome measures were pelvic pain scores for dysmenorrhoea, nonmenstrual pelvic pain (NMPP), uterine bleeding and lumbar spine bone mineral density (BMD).ResultsLinzagolix pharmacokinetics were described by a 2‐compartment model with sequential zero/first‐order absorption process (CL/F: 0.422 L/h). E2 changes over time were well described as a function of linzagolix 24‐hour AUC (AUC50: 1.68 × 105 ng h/mL). For a Caucasian reference patient, a change in E2 from 50–20 pg/mL at 24 weeks increased the odds of relief of dysmenorrhoea 1.33‐fold and NMPP 1.07‐fold (95% CI: 1.22–1.47 and 1.02–1.12, respectively) and decreased bleeding days by 1.55 (95% CI: 1.39–1.72). A previously validated quantitative systems pharmacology BMD model was adjusted to the clinical data. The mean week 24 lumbar spine BMD change from baseline ranged from −0.092% in the 50 mg dose, −1.30% in the 100 mg dose group and −2.67% in the 200 mg dose group.DiscussionThe previously‐reported E2 target range (20–50 pg/mL) to balance efficacy and safety endpoints was confirmed. Linzagolix once daily doses between 75–125 mg daily were expected to meet endometriosis‐associated pain, efficacy, and BMD loss targets in Caucasian patients.

Factors Associated with Bone Mineral Density and Bone Resorption Markers in Postmenopausal HIV-Infected Women on Antiretroviral Therapy: A Prospective Cohort Study.

The study aimed to determine factors associated with changes in bone mineral density (BMD) and bone resorption markers over two years in black postmenopausal women living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). Women (n = 120) aged > 45 years were recruited from Potchefstroom, South Africa. Total lumbar spine and left femoral neck (LFN) BMD were measured with dual energy X-ray absorptiometry. Fasting serum C-Telopeptide of Type I collagen (CTx), vitamin D and parathyroid hormone were measured. Vitamin D insufficiency levels increased from 23% at baseline to 39% at follow up. In mixed linear models serum CTx showed no change from baseline to end (p = 0.363, effect size = 0.09). Total and LFN BMD increased significantly over two years, but effect sizes were small. No significant change in spine BMD over time was detected (p = 0.19, effect size = 0.02). Age was significantly positively associated with CTx over time, and negatively with total and LFN BMD. Physical activity (PA) was positively associated with LFN BMD (p = 0.008). Despite a decrease in serum vitamin D, BMD and CTx showed small or no changes over 2 years. Future studies should investigate PA interventions to maintain BMD in women living with HIV.

Circulating Lipocalin-2 Predicts Changes in Lumbar Spine Bone Mineral Density After Parathyroidectomy in Primary Hyperparathyroidism

Lipocalin-2(LCN2), known as neutrophil gelatinase-associated lipocalin is known to a regulator of bone homeostasis. Upregulation of LCN2 in mice reduces osteoblast differentiation and stimulates the NF-kB pathway, promoting osteoclastogenesis. High serum LCN2 level was associated with elevated risk of fracture-related hospitalization in elderly women. Bone mineral density(BMD) of primary hyperparathyroidism(PHPT) patients tends to recover after parathyroidectomy, but with different extent. Whether circulating LCN2 can predict the extent of BMD recovery after parathyroidectomy in PHPT remains unclear. Clinical data and preoperative serum samples obtained from 35 PHPT patients (women n=30) who underwent parathyroidectomy at Severance hospital, Seoul, Korea between 2016 and 2019 were analyzed. Among 35 patients, 25 patients underwent BMD before surgery and two years after surgery. LCN2 was measured using enzyme-linked immunosorbent assay kit (DLCN20, R&D Systems, USA). Primary outcome was two-year lumbar spine BMD change (%). Mean age of study subjects was 57±13 years. Calcium and parathyroid hormone (PTH) levels restored to normal range after parathyroidectomy in all subjects (calcium [mean 8.7±0.4mg/dL]; PTH [median 33.3], 25.9 to 47.4 pg/mL). Baseline BMD of lumbar spine(LS), femoral neck(FN), and total hip(TH) were 0.776±0.177 g/cm2, 0.578±0.138 g/cm2, and 0.695±0.150 g/cm2, respectively. At 1 year after parathyroidectomy, BMD increased up to 5.5%, 6.1%, and 4.5% at LS, FN, and TH, respectively. At 2 years after parathyroidectomy, BMD increased up to 8.6%, 7.6%, and 7.2% at LS, FN, and TH, respectively. Log-transformed LCN2 at baseline showed positive correlation with LS BMD changes (%) after 2 years (β Coefficient = 3.46, 95% CI = 0.83 to 6.10, p-value = 0.012). In multiple linear regression model, one log-unit increment in LCN2 was associated with 4.7 percent point increase in LSBMD at two years after parathyroidectomy (adjusted β=4.72, 95% CI = 1.62 to 7.82, p-value = 0.005) after adjustment of PTH, creatinine level, and body mass index. This result remained robust for 3 year change in LSBMD (in subgroup, n=14; adjusted β=4.70, 95% CI = 0.9 to 8.5, p-value = 0.021). In conclusion, preoperative high circulating LCN2 level was associated with more LSBMD gain after parathyroidectomy in patients with PHPT.

Impact of high-load resistance training on bone mineral density in osteoporosis and osteopenia: a meta-analysis.

This study aimed to examine the effect of high-load resistance training (HLRT) on bone mineral density (BMD) in patients with osteoporosis and osteopenia using a meta-analysis. We searched for randomized controlled trials (RCTs) on HLRT in patients with osteoporosis and osteopenia from medical databases. Our meta-analysis was performed with the primary endpoints being the standardized mean difference (SMD) of the change in BMD of the lumbar spine (LS), femoral neck (FN), and total hip (TH). The robustness of the results was assessed by subgroup analysis. Heterogeneity factors were examined by meta-regression. Publication bias was evaluated using a funnel plot. We selected nine RCTs, with 259 patients in the HLRT group (women, 55.2%) and 236 patients in the control group (women, 62.7%). The HLRT group showed a significant increase in BMD in the LS [SMD = 1.40, 95% confidence interval (CI) = 0.68-2.12, p < 0.001, I2 = 90%], the FN (SMD = 0.86, 95% CI = 0.05-1.67, p = 0.04, I2 = 92%), and the TH (SMD = 1.26, 95% CI = 0.45-2.08, p = 0.002, I2 = 91%). Subgroup analysis confirmed the robustness of the results only in LS. Total sessions and a high risk of bias were identified as the factors of heterogeneity in FN and TH (p < 0.05). The funnel plot showed asymmetry in all measurement sites. This study suggested that HLRT can be effective in increasing BMD, mainly of LS, in patients with osteoporosis and osteopenia. However, due to high heterogeneity and publication bias, additional studies with a low risk of bias should be conducted to generalize our findings.

Contributions of Clinical and Technical Factors to Longitudinal Change in Trabecular Bone Score and Bone Density: A Registry-Based Individual-Level Analysis.

Lumbar spine trabecular bone score (TBS), a gray-level texture measure derived from spine dual-energy X-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved question is whether TBS is sufficiently responsive to change over time or in response to widely used osteoporosis therapy at the individual level to serve as a useful biomarker. Using the Manitoba DXA Registry, we identified 11,643 individuals age 40 years and older with two fan-beam DXA scans performed on the same instrument within 5 years (mean interval 3.2 years), of whom 6985 (60.0%) received antiresorptive osteoporosis medication (majority oral bisphosphonate) between the scans. We examined factors that were associated with a change in lumbar spine TBS, lumbar spine BMD, and total hip BMD exceeding the 95% least significant change (LSC). Change exceeding the LSC was identified in 23.0% (9.3% increase, 13.8% decrease) of lumbar spine TBS, 38.2% (22.1% increase, 16.1% decrease) lumbar spine BMD, and 42.5% (17.6% increase, 24.9% decrease) total hip BMD measurement pairs. From regression models, the variables most strongly associated with significant change in TBS (decreasing order) were tissue thickness change, acquisition mode change, weight change, and spine percent fat change. Consistent with the insensitivity of TBS to oral antiresorptive therapies, use of these agents showed very little effect on TBS change. In contrast, for both spine BMD change and total hip BMD change, osteoporosis medication use was the most significant variable, whereas tissue thickness change, acquisition mode change, and weight change had relatively weak effects. In summary, change in spine TBS using the present algorithm appears to be strongly affected by technical factors. This suggests a limited role, if any, for using TBS change in untreated individuals or for monitoring response to antiresorptive treatment in routine clinical practice with the current version of the TBS algorithm. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Long-term bone mineral density changes and fractures in lung transplant recipients with cystic fibrosis

BackgroundLittle is known about long-term bone mineral density (BMD) changes and fractures in lung transplant recipients with cystic fibrosis (CF). We examined femur and lumbar spine (LS) BMD changes in men and women with CF up to 10 years post-transplant and documented post-transplant fracture prevalence. MethodsRetrospective study of individuals who had undergone a lung transplant (2000–2015) and had a pre-transplant and at least one BMD measurement after transplant. Vertebral fractures were assessed on chest computed tomography scans and other fractures abstracted from medical records. ResultsThe cohort consisted of 131 individuals; 53% males, median age: 28 years [interquartile range: 24–35] and 31% having pre-transplant low bone mass. Most recipients were given bisphosphonates after transplant with proportion reaching 94% at 10 years. Up to 10 years post-transplant, men experienced positive or little change in LS BMD, indicating minimal loss from pre-transplant values. In contrast, women displayed negative changes in BMD up to 5 years post-transplant before recovering pre-transplant BMD values by 10 years. Similar patterns were observed at the femur BMD where men demonstrated a lower bone loss and faster recovery towards pre-transplant values than women. After transplant, 88% of recipients maintained their pre-transplant bone status, 3% experienced an improvement, mostly progressing from low bone mass to normal status whereas 9% had a deterioration of their pre-transplant bone status. Twenty-seven recipients suffered fractures in the post-transplant period. ConclusionsThese findings underline that lung recipients with CF remain at risk of skeletal fragility despite prompt initiation of post-transplant anti-osteoporosis therapy.

Short Communication: Impact of Fat Changes on the Effect of Protease Inhibitors on Lumbar Spine Bone Mineral Density Changes with Antiretroviral Therapy Initiation.

People living with HIV (PLWH) who are on protease inhibitor (PI)-containing regimens have been shown to have increases in visceral adipose tissue (VAT) and a greater decrease in spine bone mineral density (BMD) than those receiving non-PI regimens when initiating treatment. This increase in VAT has been hypothesized to falsely lower spine BMD measured via dual-energy X-ray absorptiometry, suggesting that the PI-associated BMD loss is an artefact rather than real. To test this, data collected from two completed 96-week clinical trials, AIDS Clinical Trial Group studies A5224s and A5260s, of antiretroviral therapy-naive PLWH initiating treatment with PI and non-PI-containing regimens were analyzed comparing VAT accumulation and spine BMD loss. Results showed no significant decrease in spine BMD in persons in the highest quartile (Q4) of VAT gain versus the rest of the study population (Q1-3) in either the PI and non-PI arms, suggesting that PI-associated BMD loss is not likely to be an artefact of overlying VAT.

Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials

The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes. We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy. Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r2 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction. Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials. Foundation for National Institutes of Health.

Oral Bisphosphonate Therapy for Osteogenesis Imperfecta: A Systematic Review and Meta-Analysis of Six Randomized Placebo-Controlled Trials.

ObjectiveTo assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients with osteogenesis imperfecta (OI).MethodsStudies were eligible for inclusion if they were randomized controlled trials of directly comparing oral bisphosphonate therapy with placebo‐group in OI patients. Data synthesis regarding to bone mineral density as measured by dual‐energy X‐ray absorptiometry (DEXA), decreased fracture incidence, change in biochemical markers of bone and mineral metabolism, bone histology, growth, bone pain, quality of life, and others were assessed, and meta‐analysis done when possible.ResultsFrom 98 potential references and six randomized controlled studies a total of 263 participants receiving oral bisphosphonates and 143 placebo treatments contributed data to meta‐analysis. Pooled meta‐analysis of three studies suggested that there was significant difference between bisphosphonate treated group and placebo in number of patients with at least one fracture (mean difference 0.53, 95% confidence interval 0.32–0.89, P = 0.02). Pooled meta‐analysis of two studies suggested that significant difference was noted between bisphosphonate treated group and placebo in mean percentage change in spine BMD (T‐score) (mean difference 28.43, 95% confidence interval 7.09‐49.77, P = 0.009). The similar effect was shown in the term of mean change (Z‐score) in spine BMD.ConclusionsSignificant improvement in lumbar areal BMD in patients affected with OI has been shown when treated with oral bisphosphonates, even though only a small population was enrolled. We cannot draw a definite conclusion that the increase in BMD can be translated into fracture reduction and clinical functional improvement. The optimal method, dose, type, initiation, and duration of oral bisphosphonates therapy still remains unclear. Well‐designed, adequately‐powered, placebo‐controlled RCTs investigating the effects of oral bisphosphonates on fractures reduction and improvement in quality of life in both children and adults are studied here.