Mean Change In Bone Mineral Density Research Articles

Longitudinal changes of the femoral bone mineral density from first to third trimester of pregnancy: bone health assessment by means of non-ionizing REMS technology

BackgroundThroughout the pregnancy, there is a substantial transfer of calcium from the maternal skeleton to the fetus, which leads to a transient net reduction of the maternal bone mineral density.AimsTo assess longitudinally the changes in the bone mineral density at the femoral neck between the first and third trimester of pregnancy in a cohort of healthy participants using Radiofrequency Echographic Multi Spectrometry (REMS) technology.MethodsProspective, cohort study conducted at the University hospital of Parma, Italy between July 2022 and February 2023. We recruited healthy participants with an uncomplicated singleton pregnancy before 14 completed weeks of gestation. All included participants were submitted to a sonographic examination of the femoral neck to assess the bone mineral density (and the corresponding Z-score values) using REMS at 11–13 and 36–38 weeks of pregnancy. The primary outcome was the change in the bone mineral density values at the maternal femoral neck between the first and third trimester of pregnancy.ResultsOver a period of 7 months, a total of 65 participants underwent bone mineral density measurement at the femoral neck at first and third trimester of the pregnancy using REMS. A significant reduction of the bone mineral density at the femoral neck (0.723 ± 0.069 vs 0.709 ± 0.069 g/cm2; p < 0.001) was noted with a mean bone mineral density change of − 1.9 ± 0.6% between the first and third trimester of pregnancy. At multivariable linear regression analysis, none of the demographic or clinical variables of the study population proved to be independently associated with the maternal bone mineral density changes at the femoral neck.ConclusionsOur study conducted on a cohort of healthy participants with uncomplicated pregnancy demonstrates that there is a significant reduction of bone mineral density at femoral neck from early to late gestation.

The effect of forearm rotation on the bone mineral density measurements of the distal radius.

Forearm dual-energy X-ray absorptiometry (DXA) is often performed in clinics where central DXA is unavailable. Accurate bone mineral density (BMD) measurement is crucial for clinical assessment. Forearm rotation can affect BMD measurements, but this effect remains uncertain. Thus, we aimed to conduct a simulation study using CT images to clarify the effect of forearm rotation on BMD measurements. Forearm CT images of 60 women were analyzed. BMD was measured at the total, ultra-distal (UD), mid-distal (MD), and distal 33% radius regions with the radius located at the neutral position using digitally reconstructed radiographs generated from CT images. Then, the rotation was altered from - 30° to 30° (supination set as positive) with a one-degree increment, and the percent BMD changes from the neutral position were quantified for all regions at each angle for each patient. The maximum mean BMD changes were 5.8%, 7.0%, 6.2%, and 7.2% for the total, UD, MD, and distal 33% radius regions, respectively. The analysis of the absolute values of the percent BMD changes from the neutral position showed that BMD changes of all patients remained within 2% when the rotation was between - 5° and 7° for the total region, between - 3° and 2° for the UD region, between - 4° and 3° for the MD region, and between - 3° and 1° for the distal 33% radius region. Subtle rotational changes affected the BMD measurement of each region. The results showed the importance of forearm positioning when measuring the distal radius BMD.

The effects of abaloparatide on hip geometry and biomechanical properties in Japanese osteoporotic patients assessed using DXA-based hip structural analysis: results of the Japanese phase 3 ACTIVE-J trial

SummaryDaily subcutaneous injection of 80 μg abaloparatide increased bone mineral density in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. Dual-energy X-ray absorptiometry–based hip structural analysis from ACTIVE-J data showed improved hip geometry and biomechanical properties with abaloparatide compared with placebo.PurposeAbaloparatide (ABL) increased bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. To evaluate the effect of ABL on hip geometry and biomechanical properties, hip structural analysis (HSA) was performed using ACTIVE-J trial data.MethodsHip dual-energy X-ray absorptiometry scans from postmenopausal women and men (ABL, n = 128; placebo, n = 65) at baseline and up to week 78 were analyzed to extract bone geometric parameters at the narrow neck (NN), intertrochanteric region (IT), and proximal femoral shaft (FS). Computed tomography (CT)-based BMD and HSA indices were compared between baseline and week 78.ResultsABL treatment showed increased mean percent change from baseline to week 78 in cortical thickness at the NN (5.3%), IT (5.3%), and FS (2.9%); cross-sectional area at the NN (5.0%), IT (5.0%), and FS (2.6%); cross-sectional moment of inertia at the NN (7.6%), IT (5.1%), and FS (2.5%); section modulus at the NN (7.4%), IT (5.4%), and FS (2.4%); and decreased mean percent change in buckling ratio (BR) at the IT (− 5.0%). ABL treatment showed increased mean percent change in total volumetric BMD (vBMD; 2.7%) and trabecular vBMD (3.2%) at the total hip and decreased mean percent change in BR at femoral neck (− 4.1%) at week 78 vs baseline. All the changes noted here were significant vs placebo (P < 0.050 using t-test).ConclusionA 78-week treatment with ABL showed improvement in HSA parameters associated with hip geometry and biomechanical properties vs placebo.Trial registrationJAPIC CTI-173575

SAT647 Quantifying The Effects Of Gender-Affirming Hormone Therapy On Bone Density Of Transgender Patients: Emerging Results Of A Single-center Study

Abstract Disclosure: C.M. Godar: None. S.C. De La Torre: None. O. Bonsu: None. M.K. Shakir: None. T.D. Hoang: None. Introduction: The care of transgender patients with gender-affirming hormone therapy (GAHT) is becoming increasingly common throughout the United States. Estrogen-based hormone therapy has well-known anabolic effects on bone density in post-menopausal women. Few studies have evaluated the long-term effect of exogenous estrogen or testosterone on bone density of transgender patients. Current guidelines do not suggest a recommended age of DXA screening onset or screening interval for transgender patients on GAHT, or whether to use birth gender vs. affirmed gender standards. In this single-center study, we aim to better characterize bone mineral density (BMD) patterns of transgender patients on GAHT over a 1-year period. Methods: 17 transgender patients underwent DXA scan at baseline, 6 months, and 1 year after starting GAHT. 11 transgender females on estradiol and 6 transgender males on testosterone were included. BMD, T-score, and Z-score data for lumbar spine, total hip, femoral neck, and forearm were measured. 2 patients did not receive 6-month scan, but all patients received baseline and 1-year scans. Mean BMD was calculated at all time points. Data were compared to known T-score and Z-score cutoffs for low BMD (T-score: ≥-1 normal, -1.1 to -2.4 osteopenia, ≤-2.5 osteoporosis; Z-score ≤-2 low BMD for age). Results: Mean BMD change for transgender males at 1 year was +1.8% at lumbar spine, -0.7% at femoral neck, +1.4% at total hip, and -13.3% at forearm. Mean BMD change for transgender females was +4.5% at lumbar spine, +2.8% at femoral neck, -6.9% at total hip, and +1.5% at forearm. Using male T-score standards, 1 transgender male who was osteoporotic at baseline was osteopenic at one year. Using female Z-score standards, 1 transgender female with low BMD for age achieved normal BMD at one year. Male Z-score and female T-score trends did not change any individual’s BMD categorization. Conclusion: These results suggest a trend of modest BMD improvement at lumbar spine after patients begin GAHT regardless of gender, with a pattern of worsening total hip BMD in transgender females and worsening forearm BMD in transgender males. These results are limited by a small study population that is growing as data collection continues. Further statistical analyses are needed to determine significance of our findings. Bone density increases may be attributed to hormone therapy, though it is hypothesized that correction of gender dysphoria and greater physical well-being play a role as well. For these variable BMD changes, we suggest that universal DXA screening guidelines could be considered for transgender patients after 1 year of GAHT, though a decision to treat based on abnormal results remains controversial. Studies of longer duration are needed to make conclusions on long-term bone density effects of GAHT. Presentation: Saturday, June 17, 2023

Twenty-four months of follow-up in women with rebound-associated vertebral fractures after discontinuation of denosumab: a single-centre case series.

To describe the densitometric and biochemical changes achieved with osteoactive treatment after 24months of follow-up in patients who suffered rebound-associated vertebral fractures (RAVFs) after Dmab discontinuation, and to report the occurrence of new vertebral and non-vertebral fractures. Patients with RAVFs who received retreatment (RT) for 24months were included. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH), along with C-terminal cross-linked telopeptide of type I collagen, osteocalcin, and bone alkaline phosphatase. Data were collected at the start of the RT and after 24months. Seven female patients were included. RT consisted in Dmab (n = 3), teriparatide (TPT) (n = 3) and zoledronate (Zol) (n = 1). At 24months, the mean BMD change was 2.2% at LS, 6.8% at FN and 3.8% at TH in the Dmab group, 7.5% at LS, 1.4% at FN and 3.7% at TH in the TPT group and, 5.0% at LS, 0.6% at FN and 3.9% at TH in the patient with Zol. After 24months of follow-up, no patient suffered new fractures. In this series of patients with RAVFs, we did not observe any new fractures and the BMD remained stable after 24months of RT. Future studies are needed to evaluate the most suitable treatment approach after RAVFs but these preliminary data suggest that all denosumab, zoledronate and teriparatide might be adequate options.

Student Competition (Knowledge Generation) ID 1985735

Background Individuals with chronic spinal cord injury or disease (SCI/D) are at an increased risk of lower extremity fractures. Novel interventions, including nutraceuticals and pharmacotherapy, are being explored to reduce fracture-related morbidity and mortality. Objective This retrospective cohort study aims to evaluate the effectiveness of Denosumab injections with dietary calcium and vitamin D supplements on proximaltibia bone mineral density (BMD) in adults with low bone mass and chronic SCI/D. Design/Methods Adult patients with SCI/D over age 18 years, with a baseline distal femur or proximal tibia Z-score &amp;lt;-2.0 or T-score &amp;lt;-2.5 exposed to at least three doses of Denosumab 60mcg/1ml vial injections will consent to chart abstraction. The cumulative Denosumab dose will be the exposure variable. Calcium intake and vitamin D serum levels will be recorded as effect modifiers. Age, sex, and BMI will be recorded as potential confounders. The primary outcome will be the change in proximal tibia BMD from baseline and secondarily the incidence of lower extremity fracture(s). Results/Findings Demographic and impairment characteristics of the study population will be reported using appropriate descriptive statistics. The associations between mean BMD change and Denosumab exposure will be calculated and adjusted for confounders using an appropriate univariate/multivariate model based on sample size and data distribution. Conclusion This retrospective cohort study will determine the effectiveness of Denosumab injections (with calcium and vitamin D) for maintaining or increasing proximal tibia BMD among patients with chronic SCI/D. The study findings will have a significant impact on Denosumab prescribing practices.

Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk

ObjectiveWe evaluated the efficacy of romosozumab in women from FRAME who had no prior fracture but met other criteria for very high fracture risk (VHFR). MethodsIn FRAME, postmenopausal women received romosozumab or placebo for 12 months (year 1) followed by denosumab for 12 months (year 2). In this post hoc analysis, we applied the following criteria from the American Association of Clinical Endocrinology to define VHFR: lumbar spine or total hip T-score <−3.0 and/or Fracture Risk Assessment Tool probability of major osteoporotic fracture >30% or hip fracture >4.5% to women with no fracture history at baseline (no fracture-VHFR [NF-VHFR]). Incidence of new vertebral, clinical, and nonvertebral fractures and mean bone mineral density (BMD) percentage change from baseline were assessed at years 1 and 2. ResultsOf the 7180 women in FRAME, 2825 were included in the NF-VHFR subgroup analysis. At year 1, romosozumab versus placebo reduced the incidence of new vertebral fracture (relative risk reduction [RRR]: 76%), clinical fracture (RRR: 60%), and nonvertebral fracture (RRR: 54%) (all P <.05). This fracture reduction was maintained through year 2 in women receiving the romosozumab-to-denosumab sequence versus the placebo-to-denosumab sequence for new vertebral, clinical, and nonvertebral fractures (RRR: 77%, 54%, and 46%, respectively; all P <.05). The mean BMD changes in both treatment groups were similar to those in the overall FRAME population at years 1 and 2. ConclusionRomosozumab significantly reduced vertebral, clinical, and nonvertebral fracture risk and increased the BMD more than placebo in women at VHFR.

Improvement in Glucocorticoid-Induced Osteoporosis on Switching from Bisphosphonates to Once-Weekly Teriparatide: A Randomized Open-Label Trial

This randomized, open-label, multicenter, parallel study imitating real-world clinical practice assessed the effect of switching to weekly teriparatide in patients with glucocorticoid-induced osteoporosis (GIO) with a lumbar spine/proximal femur bone mineral density (BMD) T-score ≤ -2.0 or ≤-1.0 and a fragility fracture. Forty-four patients were randomized. The mean durations of the corticosteroid and bisphosphonate administrations were 90.0 and 51.3 months. The baseline BMD at L1-L4 was 0.828 and 0.826 g/cm2 in Groups B (bisphosphonate) and T (teriparatide); at the femur (total), these values were 0.689 and 0.661 g/cm2. The mean change in BMD was numerically higher with teriparatide vs. bisphosphonate but not statistically significant. The mean percentage changes from baseline in BMD at L1-L4 after a 72-week treatment were 0.5% and 4.1% in Groups B and T. The incidence of new fractures was higher in the patients taking bisphosphonates vs. those receiving once-weekly teriparatide at 72 weeks (18.2% vs. 11.8%) and 144 weeks (22.7% vs. 17.6%). The mean percentage change in femur (trochanter) BMD (0.035 [0.007-0.063]; p = 0.02) was significantly greater with teriparatide vs. bisphosphonates. Adverse events (AEs) were more frequent with teriparatide vs. bisphosphonates. Switching to once-weekly teriparatide tended to increase lumbar spine BMD and reduce the occurrence of new fractures vs. bisphosphonates.

OR01-5 Transition From Low Dose Denosumab 30mg to IV Zoledronic Acid: Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis: A Prospective Observational Study

Abstract Introduction Cessation of denosumab(Dmab), a fully human monoclonal antibody to RANK-ligand, is associated with rises in bone remodelling, reductions in bone mineral density(BMD) and an increased fracture risk. We previously reported that BMD was stable following a switch from Dmab 60mg to 30mg in postmenopausal women with osteoporosis at a moderate fracture risk(1). The primary objective of this extension study is to evaluate the effect of switching patients from 30mg Dmab(6monthly) to IV Zoledronic acid (ZA), administered 6 months following the last dose of Dmab, in preventing bone loss in postmenopausal women with osteoporosis who are no longer at a high fracture risk. Methods Postmenopausal women with osteoporosis at a moderate or low fracture risk, previously on 30mg of Dmab 6monthly were switched to receive 5mg of IV ZA. Exclusion criteria included an additional skeletal disorder, prior fragility fracture, or use of oral steroids (daily in the past 12months). The primary endpoints were the mean percent change in BMD at the lumbar spine(LS), total hip(TH), femoral neck(FN) and 1/3radius(1/3R), as well as the percent change in alkaline phosphatase(ALP) at 24 months compared to baseline, following transition to IV ZA. Secondary outcomes were clinical fractures. Results 8 patients were included in the study. The mean duration of 30mg Dmab prior switching to IV ZA was 14.6 ± 2.8 months. Mean percent change in BMD at LS was -3.04(CI: 5.77, -0.32, p =0.033) and mean absolute change was -0.025gm/cm2(CI: -0.048, -0.002, p=0.038). The percent change at the TH was -2.64(CI: -4.97, -0.31, p=0.031) with a mean absolute change of -0.021 gm/cm2(CI: -0.040, -0.002, p=0.038). There were no statistically significant changes at the FN, or 1/3R sites at 24months post IV ZA. ALP showed 45.5% increase on average at 24months compared to baseline(95% CI: 14.1, 76.9, p=0.011). No clinical fractures were observed. Conclusions We observed a statistically significant decline in mean percent change in BMD at the LS and TH following a switch from 30mg Dmab to IV ZA at 24months following IV ZA administration. This is similar to the data seen following a switch from standard dose Dmab(60mg 6monthly) to IV ZA(2). The small decline in BMD seen maybe within the precision error of the assessment and this requires further evaluation in a larger number of patients. This was associated with a rise in ALP, however we did not observe any clinical fractures in this study.

No difference in outcome or migration but greater loss of bone mineral density with the Collum Femoris Preserving stem compared with the Corail stem: a randomized controlled trial with five-year follow-up.

The aim of this study was to compare the mid-term patient-reported outcome, bone remodelling, and migration of a short stem (Collum Femoris Preserving; CFP) with a conventional uncemented stem (Corail). Of 81 patients who were initially enrolled, 71 were available at five years' follow-up. The outcomes at two years have previously been reported. The primary outcome measure was the clinical result assessed using the Oxford Hip Score (OHS). Secondary outcomes were the migration of the stem, measured using radiostereometric analysis (RSA), change of bone mineral density (BMD) around the stem, the development of radiolucent lines, and additional patient-reported outcome measures (PROMs). There were no statistically significant differences between the groups regarding PROMs (median OHS (CFP 45 (interquartile range (IQR) 35 to 48); Corail 45 (IQR 40 to 48); p = 0.568). RSA showed stable stems in both groups, with little or no further subsidence between two and five years. Resorption of the femoral neck was evident in nine patients in the CFP group and in none of the 15 Corail stems with a collar that could be studied. Dual X-ray absorbiometry showed a significantly higher loss of BMD in the proximal Gruen zones in the CFP group (mean changes in BMD: Gruen zone 1, CFP -9.5 (95% confidence interval (CI) -14.8 to -4.2), Corail 1.0 (95% CI 3.4 to 5.4); Gruen zone 7, CFP -23.0 (95% CI -29.4 to -16.6), Corail -7.2 (95% CI -15.9 to 1.4). Two CFP stems were revised before two years' follow-up due to loosening, and one Corail stem was revised after two years due to chronic infection. The CFP stem has a similar clinical outcome and subsidence pattern when compared with the Corail stem. More pronounced proximal stress-shielding was seen with the CFP stem, suggesting diaphyseal fixation, and questioning its femoral neck-sparing properties in the long term. Cite this article: Bone Joint J2022;104-B(5):581-588.

Short-Term Analysis of the Changes in the Bone Mineral Density of the Proximal Femur After Uncemented Total Hip Arthroplasty: A Prospective Study of 110 Patients.

IntroductionMechanical loading continuously exposes the bone to remodeling processes. Increased load leads to a gain in bone mass, and reduced load results in a loss. After inserting a prosthesis, the proximal femur is bypassed in loading as the bodyweight shifts distally. This lack of load induces bone resorption according to Wolff’s law. To avoid this bone resorption, the implant's bending stiffness should be less than the femoral bone. Dual-energy X-ray absorptiometry (DEXA) is a well-accepted method to measure periprosthetic bone mineral density (BMD) after total hip arthroplasty (THA). Since the strength and durability of the fixation of a femoral prosthesis in cementless hip arthroplasty depend largely on the quantity and quality of the surrounding bone, preoperative and postoperative evaluation of the quantity and quality of the femoral bone is very important in the long-term prognosis of hip arthroplasty.Materials and methodsA prospective study of 110 patients in the age group of 25-60 years who underwent uncemented total hip arthroplasty in our tertiary healthcare institution was performed. An uncemented, fully hydroxyapatite-coated implant from a single manufacturer was used in all the patients. All the patients were mobilized on the first post-operative day. The BMD was measured at the proximal femur and the distal tip using a DEXA scan. Gruen zones were used for calculating BMD at different anatomical locations in the femur, with particular importance to zones 1, 4, and 7.ResultsThe pre-operative BMD in all zones measured, viz. zones 1, 4, and zone 7 of the affected side, was found to be significantly lower as compared to the BMD values on the control side (P< 0.05). The mean change in the mean BMD was calculated for all the zones and compared with each other using an unpaired t-test. The mean BMD changes were found to be significantly higher in zone 7 in comparison to both zones 1 and 4 (p<0.05).ConclusionSignificant periprosthetic bone loss after uncemented THA in the femur was noted in Gruen zones 1, 4, and 7 during the first six months after THA, with the greatest bone loss in the femoral calcar area (zone 7). The lower the preoperative BMD of the patient, the greater the postoperative bone loss.

Effect of lumbar spinal stenosis on bone mineral density in osteoporosis patients treated with ibandronate

BackgroundLumbar spinal stenosis (LSS) can cause various neurological symptoms and reduce the daily activity of patients. Many studies have shown that free physical activities and exercise can improve bone mineral density (BMD) in patients with osteoporosis. However, the effect of LSS on BMD has not been reported. The purpose of this study was to investigate the effects of LSS on BMD in patients treated with ibandronate for newly diagnosed osteoporosis.MethodsGroup 1 included 83 patients treated for osteoporosis alone, and group 2 included 76 patients treated for both osteoporosis and symptomatic LSS. We confirmed four BMD values presented as T-score at initial, and 1-, 2-, and 3-year follow-ups. Mean BMD and annual changes of BMD for three years were compared between the two groups. Correlations between initial BMD and total change of BMD, and related factors for continuous BMD improvement for three years were also evaluated.ResultsMean annual BMDs were significantly higher in group 1 compared than in group 2 (-3.39 vs. -3.58 at 1-year; -3.27 vs. -3.49 at 2-year; -3.13 vs. -3.45 at 3-year; all p < 0.05). Annual change of BMD at 1-year follow-up (0.32 vs. 0.21, p = 0.036) and total change of BMD for three years (0.57 vs. 0.35, p = 0.002) were significantly higher in group 1. Group 1 had a strong negative correlation (r = -0.511, P = 0.000) between initial BMD and total change of BMD, whereas group 2 showed a weak negative correlation (r = -0.247, p = 0.032). In multivariate analysis, symptomatic LSS was the only independent risk factor for continuous BMD improvement (Odds ratio = 0.316, p = 0.001).ConclusionsSymptomatic LSS may interfere with BMD improvement in the treatment of osteoporosis with ibandronate. Active treatment for LSS with more potent treatment for osteoporosis should be taken to increase BMD for patients with osteoporosis and LSS.

Preoperative imaging predicts change in bone mineral density after parathyroidectomy for primary hyperparathyroidism.

Bone Mineral Density (BMD) improves after parathyroidectomy (PTX), but data on factors that predict bone recovery are limited. No studies have evaluated if preoperative imaging findings are associated with postoperative change in BMD. We hypothesized that larger, metabolically active glands would be associated with greater increase in BMD after PTX. Patients with primary hyperparathyroidism (PHPT) who underwent combined Tc-99m sestamibi and 4D-CT imaging prior to PTX and had pre- and post-operative dual-energy X-ray absorptiometry (DXA) at our institution were considered for inclusion. Retrospectively, data were collected from imaging studies on each parathyroid gland, including estimated weight (using the ellipsoid formula) and contrast enhancement on 4D-CT as well as sestamibi avidity. Total estimated parathyroid weight was calculated. The main outcome measure was the percent change in BMD at the lumbar spine (LS) from pre- to post-operative DXA. Predictors of change in BMD at the LS were assessed. Complete DXA data was available in 25 patients. Median total parathyroid weight on 4D-CT was 270mg, and mean change in BMD at the LS was 2.4±4.3%. The increase in BMD was best predicted by higher preoperative serum calcium (p=0.01), greater estimated parathyroid weight (p=0.001), sestamibi avidity (p=0.03), and increased time between DXA scans (p=0.03) in the multivariable model (R2=0.79, p<0.0001). In PHPT, higher preoperative serum calcium, parathyroid gland weight on imaging, and sestamibi avidity are associated with greater increases in BMD after curative PTX. These findings suggest that larger, metabolically active adenomas may mobilize more calcium from bone.

Effect of long-term use of unfractionated or low-molecular-weight heparin on bone mineral density in maintenance hemodialysis patients.

ABSTRACTIntroductionLong‐term use of unfractionated heparin (UFH) or low‐molecular‐weight heparin (LMWH) causes bone loss and osteoporosis in patients not receiving hemodialysis. This study aimed to investigate the effect of UFH and LMWH on bone mineral density (BMD) in patients undergoing maintenance hemodialysis (MHD).MethodsPatients undergoing MHD using UFH or LMWH as anticoagulants were enrolled. BMD (in g/cm2), T‐score and Z‐score (BMDs) were measured at the lumbar spine and femur neck using dual‐energy X‐ray absorptiometry (DXA) at baseline and 2 years later. Patient demographics and clinical indices were collected. Correlation analysis was used to identify significant predictors of bone loss. Multiple linear regression was used to explore the relationship between heparin type and bone loss progression.FindingsA total of 104 patients were enrolled and completed the baseline BMD test; 72 completed the test again 2 years later. Six patients were excluded because they used both UFH and LMWH. Although BMD decreased in some patients in the UFH group, a slight increase in the BMD was observed on an average in the LMWH group after 2 years. The mean change in BMD (in g/cm2) [0(−0.03,0.04) vs. 0.04(0,0.06), P = 0.023], T‐score [0(−0.40,0.30) vs. 0.35(−0.03,0.53), P = 0.038], and Z‐score [0.10(−0.30,0.40) vs. 0.45(0.08,0.63), P = 0.031] in the lumbar spine in the UFH group was lower than those in the LMWH group. Femur neck BMD did not change significantly. In a linear regression model, after adjusting for diabetes mellitus, parathyroid hormone, and serum phosphate, we did not find an association between heparin substances and BMD.DiscussionUFH might be associated with loss of lumbar spine BMD in patients undergoing MHD.

Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study

Soy isoflavones are potentially beneficial phytoestrogens, but their tissue-selective effects in women are poorly understood. We tested the hypothesis that soy isoflavones affect bone mineral density (BMD), which may be influenced by individual differences in isoflavone metabolism and serum calcium levels. Ninety-nine healthy premenopausal women were randomized to isoflavones (136.6 mg aglycone equivalence) and 98 to placebo for 5 days per week for up to 2 years. BMD, serum calcium, and urinary excretion of daidzein and genistein were measured before and during treatment. In 129 adherent subjects, we found that isoflavone exposure, determined by urinary excretion levels, but not by dose assignment, interacted with serum calcium in affecting whole body BMD, but not hip and spine BMD. The regression coefficient was −0.042 for genistein excretion (GE) and 0.091 for the interaction between GE and serum calcium (all P < .05). Daidzein excretion had similar but marginal effect. Genistein significantly decreased whole body BMD only at low normal serum calcium levels but increased whole body BMD at higher serum calcium levels. Comparing maximum to minimum GE, mean changes in whole body BMD were +0.033 and −0.113 g/cm2 at serum calcium levels of 10 and 8.15 mg/dL, respectively. These associations were not evident by intention-to-treat analysis, which could not model for inter-individual differences in isoflavone metabolism. In summary, soy isoflavones decrease whole body BMD only when serum calcium is low. Isoflavones are dietary substances that may influence calcium homeostasis by releasing calcium from bone while sparing the common fracture risk sites hip and spine.

OR03-1 The Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Osteoarthritis

Abaloparatide (ABL) is a novel, selective activator of the PTH1 receptor signaling pathway. In the 18-month Phase 3 ACTIVE study in women with postmenopausal osteoporosis (OP) (NCT01343004), ABL significantly increased bone mineral density (BMD), and decreased the risk of new vertebral (VF), nonvertebral (NVF), and clinical fractures vs placebo (PBO), and major OP fractures vs teriparatide (TPTD) and PBO. The relationship between osteoarthritis (OA) and OP is unclear. However, increased risk of fragility fracture has been associated with OA despite those patients having higher than average BMD. The objective of this post hoc analysis was to evaluate the efficacy and safety of ABL in patients with OA enrolled in ACTIVE. In ACTIVE, 2,463 postmenopausal women with OP were randomized 1:1:1 to double-blind daily ABL 80 µg or PBO, or open-label TPTD 20 µg, SC for 18 months. Patients were identified as those with medical history of ongoing “osteoarthritis”, “spinal osteoarthritis”, “nodal osteoarthritis”, or “intervertebral disc degeneration.” New VF incidence was evaluated using the modified intent-to-treat (mITT) population, other efficacy endpoints were evaluated using the ITT population. The percent mean changes in BMD from baseline to 18 months were calculated for the total hip (TH), femoral neck (FN), and lumbar spine (LS). A total of 888 patients with ongoing OA were identified in three treatment groups; ABL (n=291), PBO (n=303), and TPTD (n=294) [overall median age: 70 years; range: 50-85 years; mean FN T-score: -2.10]. Most common sites of OA were at the spine (n=336, 38%) and knee (n=328, 37%). At baseline, 196 (22%) patients had a prevalent VF, 208 (23%) reported ≥1 prior NVF within the last 5 years, and 369 (42%) had no prior fractures. Percent experiencing any new VF were 0%, 5.1%, and 0.4% in ABL, PBO, and TPTD, respectively (ABL vs PBO, P<0.001). Kaplan-Meier estimated cumulative incidence for other fracture endpoints was similar across treatment groups. At 18 months, significant increases (P<0.0001) in BMD from baseline were observed for ABL vs PBO at the TH (mean change 3.17% vs -0.35%), FN (2.81% vs -0.36%), and LS (8.78% vs 0.86%), consistent with the overall ACTIVE population results. Most common TEAEs were hypercalciuria (11% vs 10.2%), dizziness (10.7% vs 6.6%), increased creatinine clearance (8.9% vs 10.6%), upper respiratory tract infection (8.6% vs 6.9%), and back pain (7.9% vs 11.6%) for ABL vs PBO groups, respectively. Among postmenopausal women with OP enrolled in ACTIVE, in a subpopulation with prevalent OA, ABL resulted in significant reduction in risk of new VF as well as significant improvements in BMD, vs PBO. Results suggest ABL may be useful in the treatment of women with postmenopausal OP and concurrent OA, at high risk for fracture. Funding: Radius Health, Inc.

Effectiveness of monthly intravenous ibandronate injections in a real-world setting: Subgroup analysis of a postmarketing observational study

ObjectivesThe favorable safety and consistent effectiveness of monthly intravenous (IV) ibandronate injections was demonstrated in a prospective, postmarketing, observational study in Japanese patients with osteoporosis. Here, we present subgroup analyses from the study. MethodsLumbar spine (L2–4) bone mineral density (BMD) gains were assessed in the following subgroups: aged <75 or ≥75 years, absence or presence of vertebral fractures, previous bisphosphonate (BP) treatment, and concomitant versus naïve osteoporosis drug treatment. The cumulative incidence of fractures and relative change in bone turnover markers were also examined. ResultsOf 1062 enrolled patients, 1025 received monthly IV ibandronate 1 mg and were assessed for 12 months. BMD gains with ibandronate were comparable, irrespective of older age or prevalent fractures. Overall, 515 patients (50.2%) had previously received osteoporosis treatment; of these, 166 (16.1%) received other BPs. Mean BMD changes were 3.69% (95% confidence interval [CI], 0.89%–6.50%) in patients previously treated with other BPs, and 4.26% (95% CI, 2.88%–5.64%) in patients who had not received prior osteoporosis treatment. Among the 510 patients (49.7%) concomitantly prescribed active vitamin D drugs, mean BMD changes were 5.74% (95% CI, 2.53%–8.95%) with eldecalcitol versus 3.54% (95% CI, 1.98%–5.10%) with ibandronate alone. The lowest fracture incidence was observed with the combination of ibandronate and eldecalcitol, but differences between the subgroups were not statistically significant. ConclusionsMonthly IV ibandronate demonstrated comparable BMD gains in the patient subgroups analyzed. Concomitant use of ibandronate with eldecalcitol showed a trend of higher BMD gains and lower fracture incidence than ibandronate alone.

Treatment with once-weekly alendronate oral jelly compared with once-weekly alendronate oral tablet for Japanese patients with primary osteoporosis: An open-label, prospective, observational study.

Background and aimsClinical data regarding alendronate jelly are limited. We compared the efficacy and safety of once‐weekly alendronate oral jelly with once‐weekly alendronate tablet formulations in the context of primary osteoporosis.MethodsIn this 6‐month, open‐label, prospective, observational study, Japanese patients aged ≥60 years with primary osteoporosis were included from 14 primary care centres in Japan. The effects of once‐weekly alendronate oral jelly and tablet formulations on bone mineral density (BMD), bone turnover markers, and quality of life related to gastrointestinal symptoms were assessed at baseline and 6 months. Treatment was allocated by patient preference. This potentially confounding factor was adjusted for statistically.ResultsIn total, 170 patients were enrolled (jelly, n = 97; tablet, n = 73). Mean percent changes in radius, lumbar spine, femoral neck, and hip BMD were similar in both treatment groups at 6 months. Both formulations decreased tartrate‐resistant acid phosphatase 5b (TRACP‐5b) and procollagen 1 N‐terminal peptide (P1NP) between baseline and 6 months (by about 50% and 60%, respectively); no significant differences in mean changes were noted in these markers between groups. At 6 months, no significant differences were noted in visual analogue scale or EuroQOL five‐dimension questionnaire scores between groups. The jelly group had significantly lower scores than the tablet group in the Izumo scale domains of heartburn (−0.81, P = 0.0040), epigastralgia (−0.94, P = 0.0003), and epigastric fullness (−0.49, P = 0.044). During treatment, more patients discontinued for upper gastrointestinal symptoms in the tablet group (n = 4) than the jelly group (n = 1).ConclusionsOnce‐weekly alendronate oral jelly 35 mg may be a suitable alternative therapeutic agent for primary osteoporosis in Japan.

Effect of 16-weeks vitamin D replacement on calcium-phosphate homeostasis in overweight and obese adults

This randomised placebo-controlled trial aimed to determine the effect of 16-weeks cholecalciferol supplementation on calcium-phosphate homeostasis and bone mineral density (BMD) in overweight and obese adults. Fifty-four vitamin D-deficient (25OHD<50 nmol/L), overweight and obese adults (mean age 32 ± 8.5 years) were included in the trial. Participants were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 weeks. Before and after the intervention, serum calcium, phosphate, 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH) and C-terminal plasma fibroblast growth factor-23 (cFGF-23) concentrations were measured. Whole-body BMD was assessed using dual-energy X-ray absorptiometry (DXA) and diet and sun exposure were assessed using self-administered questionnaires. There were no significant differences in baseline characteristics between the vitamin D and placebo group. After 16-weeks of vitamin D supplementation, mean changes in 25(OH)D concentration were higher in the vitamin D group (57 nmol/L 95% CI 49, 65) compared with placebo (2 nmol/L 95% CI -4, 8), P < 0.001. Additionally, iPTH concentrations declined in the vitamin D group (−1.19 pmol/L 95% CI −1.9, −0.47) compared with placebo (0.14 pmol/L 95% CI −0.49, 0.77), P = 0.006. There were no significant differences in calcium, phosphate, iPTH and cFGF-23 concentrations and whole-body BMD between vitamin D and placebo at follow-up. Inverse correlations were observed between mean change in serum iPTH and cFGF-23 in the vitamin D group only (r=-0.41, P = 0.029). In individuals with greater vitamin D deficiency at baseline (25(OH)D < 30 nmol/L), there was a significant increase in mean whole-body BMD (0.01 g/cm2, 95% CI 0.001, 0.025) however, the mean change in BMD was not different between vitamin D and placebo groups in this sub-group analysis. We conclude that cholecalciferol supplementation for 16 weeks increases serum 25(OH)D concentrations and reduces iPTH concentrations in overweight and obese, but otherwise healthy adults with vitamin D deficiency, and has no effect on calcium, phosphate and iFGF-23 concentrations and whole-body BMD.

The effect of glucocorticoids on bone mineral density in patients with rheumatoid arthritis: A systematic review and meta-analysis of randomized, controlled trials.

The role of glucocorticoids in the treatment of rheumatoid arthritis (RA) is widely debated. Impairment of bone formation may be counter-balanced by reduced systemic inflammation. This review aims to assess the effect of prednisolone/prednisone on bone mineral density (BMD) in patients with RA analyzed in randomized, controlled trials. We performed a systematic literature search and identified randomized, double-blinded placebo-controlled studies including patients with RA and using prednisolone or prednisone as the intervention. We selected studies that measured BMD by DXA at baseline and at least once thereafter. Two authors independently performed reference review, data extraction and risk of bias assessment. Primary outcome was mean change in BMD from baseline to follow-up. Secondary endpoints included radiographic scores, RA disease activity indices and fractures. We rated the quality of evidence using the GRADE approach. Outcomes were standardized for meta-analyses and 95% confidence intervals (95% CI) were calculated. We identified 7 studies and included previously unpublished data. Studies were similar regarding study population and intervention. Standard mean difference (SMD) in change in BMD from 0 to 24 months was -0.02 (95%CI -0.16, 0.12) at the lumbar spine and -0.11 (95% CI -0.25, 0.02) at the hip (both high quality evidence) between patients treated with prednisolone/prednisone or not. Data completeness was low in some studies, concomitant treatment of RA differed between studies and differences in use of anti-osteoporotic medication may have influenced the results. However, sensitivity analyses excluding studies in which participants used either the most or the least potent concomitant RA treatment or used anti-osteoporotic therapies did not alter the estimates. In patients with early and active RA, we found no difference in change in BMD between patients treated with prednisone/prednisolone versus placebo, suggesting that at least through 24 months, the suppression of inflammation by glucocorticoids may counterbalance their adverse effects on bone remodeling.