Changes In BMD Research Articles

Bone density changes in young women in Uganda using tenofovir-based HIV pre-exposure prophylaxis and depot medroxyprogesterone acetate contraception

Background: Injectable depot medroxyprogesterone acetate (DMPA) is the most common contraceptive choice among young women in Uganda, where HIV burden is high and HIV pre-exposure prophylaxis (PrEP) may be offered. For young women who choose to use both agents concurrently, it is unknown whether they will experience declines in BMD beyond those elicited by either product singly. Methods: From 2018–2022, we conducted a 2-year prospective study with women ages 16–25 years in Kampala, Uganda desiring pregnancy and HIV prevention. Women were provided condoms, injectable DMPA, and/or FTC/TDF, according to their choices and underwent annual dual x-ray absorptiometry (DXA) scans. We used tenofovir-diphosphate (TFV-DP) quantification in dried blood spots and DMPA injection dates to classify exposure. Linear regression models estimated the difference in % BMD change from baseline to month 12 for women using FTC/TDF and DMPA versus women using neither product. Results: Of 499 enrolled women, discontinuation and re-starting of contraception and PrEP was common. Women consistently using neither product (n = 39) experienced BMD increases. Women with consistent use of both products during 1 year (n = 22) experienced an average BMD loss of 1.04% at lumbar spine and hip and 1.77% at femoral neck. These losses were different relative to women who used neither agent: lumbar spine -3.35% (95% CI −5.13%, −1.56%, p = 0.001), total hip −2.24% (95% CI −3.87%, −0.60%, p = 0.009), and femoral neck −1.71% (95% CI −3.73%, 0.31%, p = 0.102). Conclusion: We observed a trend for women with concurrent DMPA and FTC/TDF PrEP use to have 1–3% lower BMD than unexposed women after 12 months.

7892 Longitudinal Changes in Bone Microarchitecture and Strength in Girls with Type 1 Diabetes

Abstract Disclosure: R. Dhaliwal: None. R.K. Saunders: None. M. Misra: None. M.L. Bouxsein: None. D.M. Mitchell: None. Introduction: Type 1 diabetes (T1D) confers an increased fracture risk, only partly explained by low areal bone mineral density (aBMD). We have previously shown in a cross-sectional study that bone microarchitecture is altered early in the course of T1D. The goal of this study is to evaluate how T1D influences longitudinal changes in volumetric BMD (vBMD) and microarchitecture. Methods: This is a 2-year prospective study of girls ages 10-16 years (62 with T1D and 59 controls). We used dual-energy x-ray absorptiometry (DXA) to measure aBMD, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius (7% site) and tibia (8% site) to measure vBMD and microarchitecture. We used linear mixed models to assess the effects of T1D on change in bone parameters over time, adjusting for bone age as an index of skeletal maturity, height, lean mass index (LMI), and fat mass index (FMI). Results: At baseline, mean duration of disease in T1D was 4.8 ± 3.2 years, and mean HbA1c was 8.6 ± 1.4%. The groups did not differ by age, bone age, and height, while T1D participants had higher LMI (p<0.001) and borderline higher FMI (p=0.107). Linear growth, weight gain, and changes in body composition over time did not differ between groups. Growth-mediated aBMD gains were observed in both groups at the subtotal body, total hip, femoral neck, and spine. While adjusted aBMD as well as trabecular bone score were lower in T1D, we did not observe between-group differences in changes in these endpoints over time. In both groups, at the distal radius, we observed significant increases over time in total and cortical vBMD, cortical thickness, trabecular (Tb) thickness, and estimated failure load, while cortical porosity decreased. While several microarchitectural parameters were altered in T1D participants, we did not observe significant between-group differences in changes in these measures over time. Of note, trabecular development was subtly altered, with T1D participants demonstrating a borderline significant decrease in Tb vBMD (-14.3 ± 9.0 mg HA/cm3, p=0.112) and Tb number (-0.14 ± 0.07 mm-[1], p=0.057), while control participants had no change in Tb vBMD or number, but a significant increase in Tb thickness (5.8 ± 2.5 µm, p=0.018). At the distal tibia, we observed similar overall detrimental effects of T1D at baseline. However, we did not observe between-group differences in microarchitectural change over time. Glycemic control as measured by HbA1c was not associated with changes in skeletal parameters among T1D participants. Conclusions: T1D leads to substantially altered areal and volumetric BMD as well as microarchitectural parameters in girls. While our data suggest that much of this deficit appears to occur early in the course of disease as prospective change is similar in T1D and controls, subtle changes in trabecular bone development at the radius may indicate ongoing impairment of bone accrual. Presentation: 6/3/2024

7867 Treatment-Related Changes in Total Hip Bone Mineral Density and Fracture Risk Reduction for Drugs With Different Mechanisms of Action: The FNIH-ASBMR-SABRE Project

Abstract Disclosure: T. Vilaca: None. M.T. Schini: None. A.R. Thompson: None. E. Vittinghoff: None. L. Lui: None. S.K. Ewing: None. D.C. Bauer: None. D.M. Black: None. M. Bouxsein: None. R. Eastell: Consulting Fee; Self; Immunodiagnostic Systems, CL Bio, CureTeQ, Biocon, Takeda, UCB. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Osteolabs. Speaker; Self; Pharmacosmos, Alexion Pharmaceuticals, Inc., Amgen Inc, UCB. Introduction: To date, trials of new anti-osteoporosis therapies have used fractures as primary endpoints. In the FNIH-ASBMR-SABRE project, we posited that the treatment-related change in total hip BMD (THBMD) could be used as a surrogate endpoint for fractures in future clinical trials of new osteoporosis therapies. To demonstrate this, we compiled a large dataset of individual patient data (IPD) from randomized trials and showed a strong association between the change in THBMD at 24 months and reduction in fracture risk. To further explore the use of THBMD as a surrogate endpoint, here we examine whether the association is robust across drugs with different mechanisms of action. Methods: We used IDP (n>120,000 participants) from 22 randomized, placebo-controlled, double-blind trials of osteoporosis medications (17 anti-resorptive, 3 PTH analogs, 1 odanacatib, and 1 romosozumab). We calculated the treatment-related difference (active-placebo) in mean % change in THBMD at 12, 18, and 24 months for each trial. We determined the treatment-related fracture risk reductions for the entire follow-up period, using logistic regression for radiologic vertebral fractures and Cox regression for all clinical fractures (a combination of non-vertebral and clinical vertebral fractures). We used meta-regression to estimate the study-level association (r2) between treatment-related differences in THBMD changes and fracture risk reduction, including only the 17 trials of anti-resorptive drugs and then using the entire set of 22 trials. Since there were only 3 trials of anabolic drugs, we did not perform separate analyses for the anabolic trials. Results: The r2 values were similar between all trials and antiresorptive trials only for both fracture outcomes at all time points. Specifically, for vertebral fractures, the r2 was 0.59 vs 0.70 at 12 mo, 0.69 vs 0.74 at 18 mo, and 0.73 vs 0.78 at 24 mo for all trials vs anti-resorptive trials only. For all clinical fractures, the r2 was 0.46 vs 0.51 at 12 mo, 0.64 vs 0.60 at 18 mo, and 0.71 vs 0.65 at 24 mo for all trials vs anti-resorptive trials only. Conclusion: These results demonstrate that the associations between treatment-related changes in THBMD and fracture risk reductions are robust across anti-osteoporosis therapies with varying mechanisms of action. We conclude that the treatment-related difference in THBMD change would predict fracture reduction equally well for drugs with different mechanisms of action. Presentation: 6/2/2024

The relationship between treatment-related changes in total hip BMD measured after 12, 18, and 24mo and fracture risk reduction in osteoporosis clinical trials: the FNIH-ASBMR-SABRE project.

There is a strong association between total hip bone mineral density (THBMD) changes after 24mo of treatment and reduced fracture risk. We examined whether changes in THBMD after 12 and 18mo of treatment are also associated with fracture risk reduction. We used individual patient data (n = 122 235 participants) from 22 randomized, placebo-controlled, double-blind trials of osteoporosis medications. We calculated the difference in mean percent change in THBMD (active-placebo) at 12, 18, and 24mo using data available for each trial. We determined the treatment-related fracture reductions for the entire follow-up period, using logistic regression for radiologic vertebral fractures and Cox regression for hip, non-vertebral, "all" (combination of non-vertebral, clinical vertebral, and radiologic vertebral) fractures and all clinical fractures (combination of non-vertebral and clinical vertebral). We performed meta-regression to estimate the study-level association (r2 and 95% confidence interval) between treatment-related differences in THBMD changes for each BMD measurement interval and fracture risk reduction. The meta-regression revealed that for vertebral fractures, the r2 (95% confidence interval) was 0.59 (0.19, 0.75), 0.69 (0.32, 0.82), and 0.73 (0.33, 0.84) for 12, 18, and 24mo, respectively. Similar patterns were observed for hip: r2 = 0.27 (0.00, 0.54), 0.39 (0.02, 0.63), and 0.41 (0.02, 0.65); non-vertebral: r2 = 0.27 (0.01, 0.52), 0.49 (0.10, 0.69), and 0.53 (0.11, 0.72); all fractures: r2 = 0.44 (0.10, 0.64), 0.63 (0.24, 0.77), and 0.66 (0.25, 0.80); and all clinical fractures: r2 = 0.46 (0.11, 0.65), 0.64 (0.26, 0.78), and 0.71 (0.32, 0.83), for 12-, 18-, and 24-mo changes in THBMD, respectively. These findings demonstrate that treatment-related THBMD changes at 12, 18, and 24mo are associated with fracture risk reductions across trials. We conclude that BMD measurement intervals as short as 12mo could be used to assess fracture efficacy, but the association is stronger with longer BMD measurement intervals.

Efficacy and Safety of Anti-Osteoporotic Agents across CKD Stages: A Meta-Analysis of Randomized Clinical Trials.

Osteoporosis poses a significant health concern, especially for individuals with chronic kidney disease (CKD). CKD disrupts mineral and bone metabolism, heightening the risk of fractures and complicating the management of osteoporosis. While anti-osteoporotic interventions aim to address bone health in CKD patients, ongoing research is essential to understand the comparative efficacy and safety of these medications, particularly in different CKD stages, notably in stages 4 and 5. We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials assessing the efficacy and safety of osteoporosis interventions in CKD up to June 15, 2024. The analysis utilized the pooled odds ratio (OR) along with the corresponding 95% confidence interval (CI), employing Comprehensive Meta-Analysis software, version 3.0. To assess heterogeneity in the results of individual studies, we used Cochran's Q statistic and the I2 statistic. We analyzed 12 randomized controlled trials involving 31,027 participants, revealing a significantly lower risk of vertebral fractures with anti-osteoporotic agents (teriparatide, denosumab, romosozumab, raloxifene) compared to placebo (pooled OR, 0.28 [95% CI, 0.22-0.36]). Stratification by CKD stages showed a lower risk in Stages 1-3 but no significant reduction in stages 4 and 5. Teriparatide, denosumab, and romosozumab were effective in lowering fracture risk, whereas Raloxifene showed no significant effect. The lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (denosumab, raloxifene, risedronate, alendronate, teriparatide) and placebo. However, romosozumab demonstrated a significantly greater BMD change in all kidney function categories. No reported side effects were observed in CKD stages 1-5 across the trials. Our meta-analysis highlights the effectiveness of anti-osteoporotic agents in lowering vertebral fracture risk in CKD patients, particularly in stages 1-3. However, this benefit is not apparent in stages 4 and 5, necessitating further research. Despite the absence of reported side effects in CKD patients, clinicians should carefully assess the suitability of these medications, considering individual risks and benefits.

The Study to Assess the Effectiveness of Cissus Quadrangularis among Postmenopausal Women with Osteopenia

ABSTRACT Background: Osteopenia refers to bone density that is not only normal but also not as low as that noted in osteoporosis. Osteopenia leads to osteoporosis and increases the risk of fractures. Current research is focused on agents that will prevent or slow the progression of bone loss. The Objectives of the Study: To assess the pretest and posttest levels of osteopenia among postmenopausal women, and to assess the effectiveness of Cissus quadrangularis (CQ) on postmenopausal women with osteopenia. Methodology: A true experimental study design using targeted sampling techniques was used to conduct 60 patients with osteopenia. The data were collected with the help of structured questionnaires. Confidentiality was maintained throughout the process. The data collected were analyzed using descriptive and inference statistics. Result: A total of 60 participants completed this study. The percent BMD changes in the CQ-treated groups did not differ at any site after 24 weeks compared to the placebo. Reduced bone remodeling activity was detected in both CQ-treated groups. These results correlated with the within-group comparison, which showed a continuously significant increase in both BTMs in the placebo group. Conclusion: This is the first clinical report that showed a promising effect on delaying bone loss of oral administration of CQ for 24 weeks, as indicated by a slower bone remodeling process via a reduction in BTMs. However, no change in BMD was observed.

Evaluation of bone density and microarchitecture in adult patients with X-linked hypophosphatemic rickets: A pilot longitudinal study

X-linked Hypophosphatemia (XLH) is the most common type of inherited rickets. Although the clinical features are well characterized, bone structure, mineralization, and biomechanical properties are poorly known. Our aim was to analyze bone properties in the appendicular and axial skeleton of adults with XLH. In this observational case-control study, each affected patient (N = 14; 9 females; age 50 ± 15 years) was matched by sex, age and body mass index to a minimum of two healthy controls (N = 34). Dual-energy X-ray Absorptiometry (DXA) analyses revealed that areal bone mineral density (aBMD) was higher in XLH patients at the lumbar spine (Z score mean difference = +2.47 SD, P value = 1.4 × 10−3). Trabecular Bone Score was also higher at the lumbar spine (P value = 1.0 × 10−4). High Resolution peripheral Quantitative Computed Tomography (HRpQCT) demonstrated that bone cross-sectional area was larger at the distal radius (P value = 6 × 10−3). Total and trabecular volumetric BMD were lower at both sites. Trabecular bone volume fraction was also lower with fewer trabecular numbers at both sites. However, bone strength evaluated by micro-finite element analyzes revealed unaffected bone stiffness and maximum failure load. Evaluation of bone mineralization with aBMD by DXA at the distal radius correlated with vBMD by HRpQCT measurements at both sites. PTH levels were inversely correlated with trabecular vBMD and BV/TV at the tibia. We then followed a subset of nine patients (median follow-up of 4 years) and reassessed HRpQCT. At the tibia, we observed a greater decrease than expected from an age and sex standardized normal population in total and cortical vBMD as well as a trabecularization of the cortical compartment. In conclusion, in adult patients with XLH, bone mineral density is high at the axial skeleton but low at the appendicular skeleton. With time, microarchitectural alterations worsen. We propose that noninvasive evaluation methods of bone mineralization such as DXA including the radius should be part of the management of XLH patients. Larger studies are needed to evaluate the clinical significance of BMD changes in XLH patients under conventional or targeted therapies.

Limosilactobacillus reuteri 6475 and Prevention of Early Postmenopausal Bone Loss

Daily supplementation with the probiotic Limosilactobacillus reuteri ATCC PTA 6475 (L reuteri) vs placebo has previously been demonstrated to reduce bone loss in an estrogen deficiency mice model and older women, although the magnitude of the effect was small. We hypothesized that long-term treatment with L reuteri could result in clinically relevant skeletal benefits in postmenopausal osteoporosis. To evaluate whether daily supplementation with L reuteri vs placebo could reduce early postmenopausal bone loss and whether the effects remained or increased over time during 2 years of treatment. A double-blind, randomized, placebo-controlled clinical trial was conducted between December 4, 2019, and October 6, 2022, at a single center in Gothenburg, southwestern Sweden. Participants were recruited by online advertisements, and letters were sent to 10 062 women aged 50 to 60 years. Responding women (n = 752) underwent telephone screening, resulting in 292 women being invited to a screening visit. Of those who were screened, 239 women met all inclusion criteria and had no exclusion criteria. Capsules with L reuteri in 2 doses, 5 × 108 (low dose) or 5 × 109 (high dose) colony-forming units, taken twice daily or placebo were administered. All capsules also included cholecalciferol, 200 IU. The primary outcome was the relative change in tibia total volumetric bone mineral density (vBMD) over 2 years. Secondary outcomes included relative change in areal BMD of the lumbar spine and total hip, bone turnover markers C-terminal telopeptide cross-links of collagen type I and type I procollagen intact N-terminal propeptide, as well as tibia trabecular bone volume fraction and cortical vBMD. Both intention-to-treat and per-protocol analyses were conducted. A total of 239 postmenopausal women (median age, 55 [IQR, 53-56] years) were included. Tibia vBMD (primary outcome), hip and spine vBMD, and tibia cortical area and BMD decreased significantly in all groups, with no group-to-group differences (percent change tibia vBMD high dose vs placebo least-squares means, -0.08 [95 CI, -0.85 to 0.69] and low dose vs placebo least-squares means, -0.22 [95% CI, -0.99 to 0.55]). There were no significant treatment effects on any other predefined outcomes. A prespecified sensitivity analysis found a significant interaction between body mass index (BMI) and treatment effect at 2 years. No significant adverse effects were observed. In this randomized clinical trial of 239 early postmenopausal women, supplementation with L reuteri had no effect on bone loss or bone turnover over 2 years. The observed interaction between BMI and treatment effect warrants further investigation. ClinicalTrials.gov Identifier: NCT04169789.

Pre-treatment bone mineral density and the benefit of pharmacologic treatment on fracture risk and BMD change: analysis from the FNIH-ASBMR SABRE project.

Some osteoporosis drug trials have suggested that treatment is more effective in those with low BMD measured by DXA. This study used data from a large set of randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. Participants were stratified into FN BMD T-score subgroups (≤-2.5, > -2.5). We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes and logistic regression for the radiographic vertebral fracture outcome. We also performed analyses based on BMD quintiles. Overall, 42% had a FN BMD T-score ≤ -2.5. Treatment with anti-osteoporosis drugs led to significant reductions in fractures in both T-score ≤ -2.5 and > -2.5 subgroups. Compared to those with FN BMD T-score > -2.5, the risk reduction for each fracture outcome was greater in those with T-score ≤ -2.5, but only the all-fracture outcome reached statistical significance (interaction P = .001). Results were similar when limited to bisphosphonate trials. In the quintile analysis, there was significant anti-fracture efficacy across all quintiles for vertebral fractures and with greater effects on fracture risk reduction for non-vertebral, all, and all clinical fractures in the lower BMD quintiles (all interaction P ≤ .03). In summary, anti-osteoporotic medications reduced the risk of fractures regardless of baseline BMD. Significant fracture risk reduction with treatment for 4 of the 5 fracture endpoints was seen in participants with T-scores above -2.5, though effects tended to be larger and more significant in those with baseline T-scores <-2.5.

Bisphosphonates Maintain BMD after Sequential Teriparatide and Denosumab in Premenopausal Women with Idiopathic Osteoporosis.

We previously reported that sequential teriparatide followed by denosumab substantially increases BMD in premenopausal idiopathic osteoporosis (PremenIOP). To determine whether administration of bisphosphonates after denosumab cessation is associated with stable BMD in PremenIOP. Open-label extension study. 24 PremenIOP Teriparatide-Denosumab Study participants. Oral alendronate (ALN), 70mg weekly, or IV zoledronic acid (ZOL), 5mg once (patient choice), was administered 7 months (M) after final denosumab dose. BMD by DXA and serum C-telopeptide (CTX) q6M; vertebral fracture assessment (VFA) and HR-pQCT q12M. 24 women with PremenIOP (aged 43 ± 8 years), severely affected with low trauma adult fractures (range 0-12; 9 with vertebral fractures) and/or very low BMD, had large BMD increases on sequential teriparatide-denosumab (spine: 25 ± 9%; total hip: 11 ± 6%). During the Bisphosphonate Extension, mean BMD and CTX changes in the entire group were small and not statistically significant at 6 or 12M.Women choosing ZOL (n = 6) versus ALN (n = 18) did not differ by baseline age, BMI, fractures, BMD, or CTX. On ZOL, there were small LSBMD declines and CTX increases, particularly between 6M and 12M, while greater stability was observed on ALN.Changes in BMD and CTX did not differ by duration of denosumab (36M vs <36M) or between 20 women who remained premenopausal and 4 who transitioned into menopause. Higher pre-teriparatide CTX, likely reflecting baseline remodeling status, predicted more spine and hip bone loss. No new vertebral (clinical or VFA screening) or non-vertebral fractures occurred. BMD remained stable in women with PremenIOP who received bisphosphonates after sequential teriparatide-denosumab therapy.

Comparative analysis of anti-osteoporosis medications in preventing vertebral body fractures after balloon kyphoplasty.

To determine optimal anti-osteoporosis medications, we compared romosozumab and teriparatide to alendronate as a control from perioperative BKP to the 1st postoperative year for treatment and secondary fracture prevention in osteoporosis. A total of 603 patients who underwent initial BKP for osteoporotic vertebral fractures were evaluated and categorized into five groups based on drug administration: romosozumab (group R, 155 patients), twice-weekly teriparatide (group TW, 48), weekly teriparatide (group W, 151), daily teriparatide (group D, 138), and alendronate (control) (group C, 111). The 1-year incidence of SVBFs, BMD change rate, and probability of requiring BKP were compared among the groups. SVBF incidence was 3.9%, 6.5%, 8.3%, 6.0%, and 14.4% in groups R, D, TW, W, and C, respectively, with all other groups exhibiting significantly lower rates than group C. The groups that administered the anabolic agents had a notably lower incidence of distant fractures than group C. Compared with group C, group R showed significantly higher BMD change rates in lumbar vertebral bodies at 4, 8, and 12months and group D at 12months. Anabolic agent groups exhibited significantly higher improvement rates than group C after conservative treatment alone. The anabolic agents were found to be more effective at reducing the incidence of SVBF (especially distant vertebral fractures) than alendronate. These agents decreased the rate of repeat BKP even after the occurrence of a fracture. Overall, the use of an anabolic agent for the treatment of osteoporosis after BKP is better than the use of alendronate, even when treatment is initiated in the perioperative stage.

Influence of age on the efficacy of pharmacologic treatments on fracture risk reduction and increases in BMD: RCT results from the FNIH-ASBMR-SABRE project.

There is a common belief that antiosteoporosis medications are less effective in older adults. This study used data from randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments and their effects on BMD differ in people ≥70 compared to those <70yr. We used individual patient data from 23 RCTs of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. We assessed the following fractures: radiographic vertebral, non-vertebral, hip, all clinical, and all fractures. We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes, logistic regression for the radiographic vertebral fracture outcome, and linear regression to estimate treatment effect on 24-mo change in hip and spine BMD in each age subgroup. The analysis included 123 164 (99% female) participants; 43% being ≥70yr. Treatment with anti-osteoporosis drugs significantly and similarly reduced fractures in both subgroups (eg, odds ratio [OR] = 0.47 and 0.51 for vertebral fractures in those below and above 70yr, interaction P = .19; hazard ratio [HR] for all fractures: 0.72 vs 0.70, interaction P = .20). Results were similar when limited to bisphosphonate trials with the exception of hip fracture risk reduction which was somewhat greater in those <70 (HR = 0.44) vs ≥70 (HR = 0.79) yr (interaction P = .02). Allocation to anti-osteoporotic drugs resulted in significantly greater increases in hip and spine BMD at 24mo in those ≥70 compared to those <70yr. In summary, anti-osteoporotic medications similarly reduced the risk of fractures regardless of age, and the few small differences in fracture risk reduction by age were of uncertain clinical significance.

Estimating Lumbar Spine Least Significant Change for Fewer than Four Vertebrae: The Manitoba BMD Registry

Introduction: The International Society of Clinical Densitometry recommends omitting lumbar vertebrae affected by structural artifact from spine BMD measurement. Since reporting fewer than 4 vertebrae reduces spine BMD precision, least significant change (LSC) needs to be adjusted upwards when reporting spine BMD change based on fewer than 4 vertebrae.Methodology: In order to simplify estimating LSC from combinations of vertebrae other than L1-L4 (denoted LSCL1-4 ), we analyzed 879 DXA spine scan-pairs from the Manitoba BMD Program's ongoing precision evaluation. The additional impact on the LSC of performing the second scan on the same day vs different day was also assessed.Results: LSC progressively increased when fewer vertebrae were included, and also increased when the scans were performed on different days. We estimated that the LSCL1-4 should be adjusted upwards by 7 %, 24 % and 65 % to approximate the LSC for 3, 2, or 1 vertebral body, respectively. To additionally capture the greater LSC when the precision study was done on different days, LSCL1-4 derived from a precision study where scans were done on the same day should be adjusted upwards by 39 %, 60 % and 112 % for 3, 2, or 1 vertebral body, respectively.Conclusion: LSCL1-4 derived from a precision study where scans are performed on the same day can be used to estimate LSC for fewer than 4 vertebrae and for scans performed on different days.

Physical development and bone mineral density of children with inflammatory bowel diseases

Relevance. Inflammatory bowel diseases can cause a lag in physical development and a decrease in the nutritional status of children. Therapy with glucocorticosteroids can aggravate the process of formation of the body and reduce the mineralization of bone tissue.Materials and methods. The study included 24 children aged 5 to 17 years with inflammatory bowel diseases, of which 19 patients did not use glucocorticosteroids in therapy – group 1, and group 2–5 children on hormone therapy. The groups did not differ statistically significantly in age and gender composition. In order to assess the level of physical development, an assessment of anthropometric indicators was carried out using the ANTHRO Plus program. Bone mineral density was assessed by densitometry. Statistical processing was carried out using Statistica 6.0 statistical programs and descriptive statistics methods. To compare independent groups of small volume, the method was used Mann-WhitneyResults. The evaluation of length, body weight and body mass index was carried out, as a result, it was found that the majority of patients who participated in the study had an average level of physical development in the population, no statistically significant differences were found by any criterion (p &gt; 0.05). When assessing the BMD in children with IBD who did not use hormone therapy in the treatment of diseases, it was found that the Z-Score level within the reference values was observed in 57.9% (n = 11) children, 1 (5.3%) child has below –2.49 and in 36.8% (n = 7) the Z-Score level was determined in the range from –1.00 SD to –2.49 SD. More than half of the patients in group 2 had no changes in BMD (60%; n = 3), the Z-Score value in 1 (20%) patient corresponded to the level of osteopenia and in 1 (20%) child – osteoporosis. No differences were found between the groups and depending on physical development, gender or age (p &gt; 0.05).Conclusions. It was found that children, regardless of the use of hormone therapy they have similar indicators in the levels of physical development and bone mineralization. The importance of monitoring the studied indicators for the timely prevention of changes is noted.

Primary Hyperparathyroidism: Assessment of the Effects of Parathyroidectomy Using Dual X-Ray Absorptiometry, Trabecular Bone Score, and Dual X-Ray Absorptiometry–Based Three-Dimensional Modeling

ObjectiveThis study aimed to evaluate the bone microstructure to determine whether curative surgery of primary hyperparathyroidism produces changes in bone mineral density (BMD), trabecular bone score (TBS), and three-dimensional (3D) dual x-ray absorptiometry (DXA) parameters and whether these changes are comparable. MethodsWe retrospectively studied 85 patients (60 women and 25 men, 60.4 ± 12.5 years) diagnosed with primary hyperparathyroidism and undergoing parathyroidectomy. Mean percent changes in BMD (lumbar spine [LS], femoral neck [FN], total hip [TH], and 1/3 radius), TBS and 3D-DXA parameters (trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical surface density (sBMD), and cortical thickness at TH) after surgery (12, 24, and/or 36 months) were calculated and compared, and we sought the determinants of these changes. ResultsAfter parathyroidectomy, BMD presented statistically significant mean increases in LS, FN, and TH during the first 3 years after surgery (P < .001), accompanied by an improvement in all 3D-DXA parameters, but there were no significant changes in 1/3 radius BMD or TBS. Cortical sBMD, trabecular vBMD, and integral vBMD reached mean increases of similar magnitude to those of FN and TH BMD. Age and preoperative serum levels of parathyroid hormone and carboxy-terminal telopeptide of type 1 collagen were significantly associated with percent changes after surgery. ConclusionWe found a benefit of parathyroidectomy for bone, with significant percent increases in LS, FN, and TH BMD up to the third year after surgery, and a qualitative benefit for the hip in both its trabecular and cortical compartments and bone strength.

Comparison of the Efficacy of Romosozumab and Teriparatide for the Management of Osteoporotic Vertebral Compression Fractures.

Romosozumab is increasingly employed to manage osteoporosis. However, no studies have analyzed its effects on recent osteoporotic vertebral compression fractures (OVCFs). Therefore, this study aimed to evaluate the efficacy of romosozumab compared with teriparatide in managing OVCFs. The electronic medical records of postmenopausal patients with recent OVCFs who were administered romosozumab or teriparatide for one year from March 2018 to August 2022 were retrospectively reviewed. We compared the 2 groups for demographics, radiological outcomes (compression ratio, Cobb angle, and bone mineral density [BMD]), and clinical outcomes (Numerical Rating Scale [NRS] for back pain). Fifty-five patients with OVCFs, 32 patients treated with romosozumab and 23 with teriparatide, were included in this study. The change of BMD (g/cm2) values was significantly higher (p = 0.016) in the romosozumab (0.04 ± 0.06) than in the teriparatide group (0.00 ± 0.08) in the femur total. Furthermore, in subgroup analysis, the change of BMD (g/cm2) values in the lumbar spine was significantly higher (p = 0.016) in the romosozumab (0.12 ± 0.06) than in the teriparatide group (0.07 ± 0.06) in the lumbar spine. The decrease in NRS was significantly higher (p = 0.013) in the romosozumab (6.6 ± 2.0) than in the teriparatide group (5.5 ± 2.1). However, there was no significant difference in radiologic outcomes between the 2 groups. Our findings suggest that romosozumab may be more effective than teriparatide in treating OVCFs in postmenopausal females, particularly in improving BMD and reducing back pain as measured by NRS.

Effects of short- and long-term TSH suppression on lumbar bone mineral density in both genders using PET/CT

Iatrogenic subclinical hyperthyroidism is induced intentionally in patients with differentiated thyroid cancer to reduce the risk of tumor recurrence. This retrospective study aimed to investigate the effect of thyroid-stimulating hormone (TSH) suppressive therapy on bone mineral density in men and women. Two cohorts of endocrine cancer patients were compared. In cohort A, 42 patients with long-lasting suppressed serum TSH were assessed. Cohort B consisted of 41 euthyroid patients. Bone density was measured in the L1-L4 lumbar vertebrae of all patients using PET/CT scans performed for cancer staging. In 17 patients of cohort A who received a second PET/CT scan, bone density was measured again to provide longitudinal analysis. A non-significant difference in age (p = .572) and equal distribution of sex (p = .916) was determined when comparing both cohorts. A significant difference (p = .011) with a moderate effect (η2 = .08; 20.4%) was observed regarding higher bone mineral density (BMD^HU) in cohort B with normal TSH levels (M 160.63 ± 54.7 HU) versus cohort A under TSH suppression therapy (M 127.9 ± 59.5 HU) for a mean duration of 4.45 ± 2.64 years. Furthermore, no significant change in BMD^HU (p = .786) was found in those patients who received a second PET/CT scan after a mean observation time of 2.3 ± 1.2 years. In conclusion, long-lasting TSH suppression therapy caused a statistically significant decrease in BMD^HU while short-lasting therapy didn't. Therefore, we can assume a higher likelihood of osteoporosis in those patients under prolonged TSH suppression.

Differential effect of atorvastatin and pravastatin on thoracic spine attenuation: A sub-analysis of a randomized clinical trial

BackgroundStatins reduce cardiovascular events and may improve bone mineral density. MethodsWe conducted a sub-analysis of a randomized clinical trial that investigated the differential effect of moderate vs intensive low-density lipoprotein cholesterol (LDL-C) lowering therapies on coronary artery calcium (CAC) scores, and used the acquired images to assess the change in radiological attenuation of selected thoracic vertebrae. Baseline and 12-month unenhanced chest CT scans were performed in 420 hyperlipidemic, postmenopausal women randomized to atorvastatin (ATV) 80 mg/day or pravastatin (PRV) 40 mg/day in the Beyond Endorsed Lipid Lowering with Electron Beam Tomography Scanning (BELLES) trial. Bone attenuation was measured in three contiguous thoracic vertebrae at baseline and 12 months. ResultsThere were no differences in baseline demographic and clinical characteristics between treatment arms. The median percent lowering (interquartile range) in LDL-C was significantly greater with ATV than PRV [-53 (-69 to 20)% vs −28 (-55 to 74)%, p < 0.001], although the CAC score change was similar [12 (-63 to 208)% vs 13 (-75 to 358)%; p = 0.44]. At follow-up, the median bone attenuation loss was significantly greater with PRV than with ATV [-2.6 (-27 to 11)% vs 0 (-11 to 25)%; p < 0.001]. The attenuation loss in the PRV group was comparable to that of a historical untreated general population sample. In the entire cohort, the changes in LDL-C and total cholesterol were inversely correlated with bone attenuation change (p < 0.01). In adjusted multivariable linear regression analyses, race and percent change in LDL-C were independent predictors of bone attenuation change. Age, body mass index, history of smoking, diabetes mellitus, hypertension, peripheral vascular disease, or hormone replacement therapy did not affect percent change in BMD. ConclusionsThese findings support the hypothesis that there is an interaction between bone and cardiometabolic health and that intensive lipid lowering has a beneficial effect on bone health.

Skeletal Manifestations, Bone Pain, and BMD Changes in Albanian Type 1 Gaucher Patients Treated with Taliglucerase Alfa

Gaucher disease is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunctions in multiple organs. Bone involvement is one of the most prevalent aspects of Gaucher disease. Pain, disability, and reduced quality of life remain the most frequent characteristics of bone involvement in Gaucher patients. Patients and Method. In this study, we will take into consideration data from 24 patients diagnosed with type 1 Gaucher disease. We followed them closely for six years in progress. At baseline, all patients started therapy with taliglucerase alfa at a mean dosage of 45 UI/kg; later, during the study, two of them switched their cure toward velaglucerase alfa. Before baseline evaluations, 12 patients had been treated with imiglucerase at variable duration times. At baseline, we performed an X-ray of long bones and the spine, and each year, different standard assessments were performed, such as bone pain, MRI of the vertebral spine and pelvis, and DEXA for bone density. Four patients left the study for various reasons, two of them at baseline and two others during year 3 (FU3). Results. At baseline, we had 8 children and 16 adults. The average age was 28.7 ± 16.5 SD years. The most frequent skeletal manifestations in our patients were reduction of tibial femoral space (40%), osteonecrosis (36%), and body vertebral reduction (32%). At baseline, 15 patients presented with bone pain to different degrees. Over the years, bone pain in our patients had a gradual improvement. The most dramatic bone pain improvement was seen in a patient who presented bone crises. Another impressive finding was a significant BMD improvement during six years of treatment. Our study showed a significant improvement in BMD comparing FU5 and baseline values ( p = 0.0007). Especially children demonstrated a significant improvement in BMD ( p = 0.00061) compared to adults ( p = 0.3673). Mean BMD change was more indicative in switched patients ( p = 0.0142) compared to naïve patients ( p = 0.147). Conclusions. Skeletal manifestations are very different in Gaucher type 1 patients. In our study, as a result of long-term evaluations, it was noticed that the most frequent skeletal manifestation was a reduction of tibiofemoral space. Bone pain has gradually improved in all patients. Also, BMD values have been enhanced over six years of treatment, especially in children.

Association Between CTSK Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density.

The aim of this study was to explore the association between CTSK polymorphisms and the response to alendronate treatment in postmenopausal Chinese women with low bone mineral density. In this study, 460 postmenopausal women from Shanghai were included. All of them were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for a year. Four tag single nucleotide polymorphisms (SNPs) in CTSK gene were genotyped. Bone mineral densities of lumbar spine (L1-L4), femoral neck and total hip were measured at baseline and after 12 months of treatment, respectively. After 1-year of treatment, there was no significant differences in BMI between baseline and follow-up. After alendronate treatment, the BMD of L1-4, femoral neck and total hip all increased significantly (all P < 0.001), with average increases of 4.33 ± 6.42%, 1.85 ± 4.20%, and 2.36 ± 3.79%, respectively. There was no significant difference in BMD at L1-L4, the femoral neck and total hip between different genotype groups at baseline (P>0.05). After 1-year treatment with alendronate, rs12746973 and rs10847 were associated with the % change of BMD at L1-L4 (P=0.038) and % change of BMD at femoral neck (P=0.038), respectively. Furthermore, rs10847 was associated with BMD response at femoral neck (P=0.013). However, the associations were not significant after Bonferroni correction. We concluded that the common variations of CTSK gene were potentially associated with the therapeutic response to alendronate treatment in Chinese women with low bone mineral density. However, further validation is needed.