scholarly journals SUN-333 Burosumab Improves Bone Density in Patients with X-Linked Hypophosphatemia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Keerti Murari ◽  
Karl Leonard Insogna
Keyword(s):  
Trabecular Bone ◽  
Human Monoclonal Antibody ◽  
Phase Iii ◽  
Mineral Density ◽  
Paired Data ◽  
Total Hip ◽  
Skeletal Mass ◽  
Significant Difference ◽  
Hip Bmd ◽  
The Impact

Abstract Background: X-linked hypophosphatemia (XLH) causes rickets in children and osteomalacia in adults due to lifelong renal phosphate wasting that is mediated by high circulating levels of FGF-23. Burosumab, is a recently approved fully human monoclonal antibody that blocks FGF23, thereby correcting the renal phosphate leak, improving mineral metabolism and reducing osteomalacia by 50-75% in adults [1]. Whether this results in measurable changes in skeletal mass and microarchitecture is unclear. Objective: We examined the impact of burosumab on regional bone mineral density (BMD) and trabecular bone scores (TBS) in study subjects involved in two phase III clinical trials of burosumab. Methods: In these trails subjects received burosumab 1 mg/kg every 4 weeks. Some patients received placebo for the first 6 months of one trial so we considered their month 6 data as their baseline. Most of the patients had been treated at some point in the past with calcitriol and phosphorus. DXA and TBS were obtained at baseline and then after 6, 12 and 18-24 months of drug treatment. Paired t-tests and ANOVA were performed to assess changes in L-spine BMD, Total Hip BMD and TBS. Results: 25 subjects with XLH (mean age 38.9 years, 56% female) were enrolled in these studies. Paired data were available in 23 subjects at 6 months, 15 subjects at 12 months and 18 subjects at 18-24 months. Compared to baseline, there were significant increases in L-spine BMD at all time points by paired analysis: 6 months (+6.0%, p=<0.0001), 12 months (+6.95%, p=<0.0001), 18-24 months (+6.13%, p=0.0005). Although there was no significant difference in total hip BMD at 6 months when compared to baseline, there were significant increases at 12 months (+6.72%, p=0.0005) and a further increase at 18-24 months (+10.02%, p=0.0029). When all available subjects were analyzed by one-way ANOVA, there was a significant effect of time of treatment on these regional BMD measurements. There was no change in trabecular bone score over the course of treatment. Conclusion: Treatment with burosumab is associated with a marked improvement in BMD, particularly in the hip. Since the hip is a frequent site of fracture in XLH, the effect of burosumab at this site is of considerable clinical relevance. The lack of an effect on TBS may relate to the fact that this measurement is much less sensitive to therapeutic interventions than BMD assessed by DXA. References: [1] JBMR. 2019. https://doi.org/10.1002/jbmr.3843.

scholarly journals The Local Concentration of Ca2+ Correlates with BMP7 Expression and Osseointegration in Patients with Total Hip Arthroplasty

2020 ◽  
Author(s):  
Xiaodong Fu ◽  
Weili Wang ◽  
Xiaomiao Li ◽  
Yingjian Gao ◽  
Hao Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Femoral Head ◽  
Total Hip Arthroplasty ◽  
Hip Arthroplasty ◽  
Local Concentration ◽  
Mineral Density ◽  
Gruen Zone ◽  
Total Hip ◽  
Significant Difference ◽  
The Impact

Abstract Background A successful osseointegration of total hip arthroplasty (THA) relies on the interplay of implant surface and bone marrow microenvironment. This study was undertaken to investigate the impact of perioperative biochemical molecules (Ca 2+ , Mg 2+ , Zn 2+ , VD, PTH) on the bone marrow osteogenetic factors (BMP2, BMP7, Stro-1 + cells) in the metaphyseal region of the femoral head, and further on the bone mineral density (BMD) of Gruen R3. Methods Bone marrow aspirates were obtained from the discarded metaphysis region of the femoral head in 51 patients with THA. Flow cytometry was used to measure the Stro-1 + expressing cells. ELISA was used to measure the concentrations of bone morphologic proteins (BMP2 and BMP7). The perioperative concentrations of the biochemical molecules above were measured by radioimmunoassay. The BMD of Gruen zone R3 was examined at 6 months after THA, using dual-energy X-ray absorptiometry (DEXA). Results Our data demonstrated that the concentration of Ca 2+ was positively correlated with BMP7 expression, and with the postoperative BMD of Gruen zone R3. However, the concentration of Mg 2+ had little impact on the R3 BMD, although it was negatively correlated with the expression of BMP7. The data also suggested that the other biochemical molecules, such as Zn 2+ , VD, and PTH, were not significantly correlated with any bone marrow osteogenetic factors (BMP2, BMP7, Stro-1 + cells). The postoperative R3 BMD of patients of different gender and age had no significant difference. Conclusions These results indicate the local concentration of Ca 2+ may be an indicator for the prognosis of THA patients.

Effect of anastrozole on bone mineral density: 5-year results from the ’Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 511-511 ◽  
Author(s):  
R. E. Coleman
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Bone Mineral ◽  
Treatment Effect ◽  
Mineral Density ◽  
Total Hip ◽  
Slowing Down ◽  
Significant Difference ◽  
Hip Bmd

511 Background: Since reporting the 1- and 2-year results from the ATAC trial bone sub-protocol, 68-month analysis results from the main ATAC trial have shown that, for postmenopausal women with invasive primary breast cancer, adjuvant treatment with anastrozole results in superior efficacy and tolerability compared with tamoxifen. Here we report 5-year bone mineral density (BMD) results from the monotherapy arms (anastrozole, n=81; tamoxifen, n=86) of the bone sub-protocol. Methods: Lumbar spine and total hip BMD were assessed by dual-energy X-ray absorptiometry at baseline and after 1, 2, and 5 years. Results: The median percentage changes in BMD at 1, 2, and 5 years, respectively, are shown in the table . Percentage changes in BMD from baseline to 5 years showed a statistically significant difference in favor of tamoxifen for both lumbar spine (treatment effect [percentage decrease of BMD on anastrozole relative to tamoxifen] −8.1; 95% confidence intervals [CI] −10.1, −6.1; p<0.0001) and total hip (treatment effect −7.4; 95% CI −9.6, −5.3; p<0.0001). For patients with data at baseline, 2, and 5 years, the rate of loss of lumbar spine BMD in the anastrozole group was significantly less from 2 to 5 years than from baseline to 2 years (mean difference in annual rate of change 0.0113, 95% CI 0.006, 0.017; p=0.0002), but there was no evidence of slowing down in the loss of total hip BMD. Five patients with osteopenia at baseline developed osteoporosis on treatment with anastrozole (4) or tamoxifen (1). No patients with normal BMD at baseline became osteoporotic at 5 years. Conclusions: Significant bone loss occurred throughout the 5 years in the anastrozole group, although there appeared to be a slowing down of the rate of bone loss in years 2–5. Although no patients with normal BMD at baseline had become osteoporotic at 5 years, regular monitoring of BMD and bone protection strategies are likely to be required in patients receiving anastrozole in the presence of pre-existing osteopenia. [Table: see text] [Table: see text]

scholarly journals The Impact of Serum C-peptide Level on Bone Mineral Density in Postmenopausal Type 2 Diabetic Women.

2019 ◽  
Vol 6 (9) ◽  
pp. 166-172
Author(s):  
Berna İmge Aydoğan ◽  
Adile Begüm Bahçecioğlu Mutlu ◽  
Çağlar Keskin ◽  
Funda Seher Özalp Ateş ◽  
Sevim Güllü
Keyword(s):  
Bone Mineral Density ◽  
Mineral Density ◽  
C Peptide ◽  
Total Hip ◽  
Peptide Level ◽  
Hip Bmd ◽  
The Mean ◽  
The Impact ◽  
Type 2 Diabetic

Objective: Recent studies suggested that c-peptide had biological activity on bone metabolism. We aimed to evaluate the impact of c-peptide level on bone mineral density (BMD) in postmenopausal type 2 diabetic women. Methods: Thirty-five insulin naïve type 2 diabetic postmenopausal women were included in our prospective cohort study. Fasting and random c-peptide, parathyroid hormone (PTH), vitamin D, insulin, alkaline phosphatase level (ALP) levels and BMD were evaluated. Results: The mean age of patients was 61.8±8.56 years. The mean fasting c-peptide, random c-peptide and insulin levels were 3.0±1.24, 7.7±3.7 and 13.9±11.2 µIU/ml, respectively. The mean femoral neck (FN-BMD) and total lumbar spine bone mineral density (L-BMD) were 0.787±0.127 and 0.919±0.122 g/cm2, respectively. C-peptide level was associated with total hip BMD (p<0.05) but this relation disappeared after regression analysis adjusted for confounders. A negative correlation between PTH level and FN-BMD was found (p=0.01). Total hip BMD and L-BMD were negatively correlated with age (p=0.01 and p=0.02, respectively). A positive association between DPP4 inhibitor treatment and total hip BMD was observed (p=0.03). Conclusions: We observed a positive association between total hip BMD and serum c-peptide level. However, this relationship disappeared in multiple linear regression analysis. Further studies are necessary to evaluate the impact of c-peptide level on the risk of osteoporosis in T2DM.

scholarly journals Changes in Adipose Tissue Distribution and Association between Uric Acid and Bone Health during Menopause Transition

2019 ◽  
Vol 20 (24) ◽  
pp. 6321 ◽  
Author(s):  
Gloria Bonaccorsi ◽  
Alessandro Trentini ◽  
Pantaleo Greco ◽  
Veronica Tisato ◽  
Donato Gemmati ◽  
...  
Keyword(s):  
Uric Acid ◽  
Postmenopausal Women ◽  
Bone Health ◽  
Positive Association ◽  
Epidemiological Studies ◽  
Mineral Density ◽  
Total Hip ◽  
Hip Bmd ◽  
Menopause Transition ◽  
The Impact

Despite convincing experimental evidence, epidemiological studies on the effects of serum uric acid (SUA) on bone health are still conflicting since factors influencing SUA bioavailability have not been adequately considered. To shed some light on this issue, we investigated the impact of adiposity and menopause status on the relationship between SUA and bone health. We examined SUA in relation to bone mineral density (BMD) at different skeletal sites and with markers of bone metabolism in 124 pre-menopausal and 234 post-menopausal women and assessed whether adiposity, evaluated by anthropometry and dual x-ray absorptiometry (DXA), might have a discriminant role. After conservative adjustment (covariates: age, hormones treatment, smoking and time since menopause), SUA showed a significant and positive association with total hip BMD (β = 0.220, p < 0.01) among postmenopausal women, maintained also after adjustment for legs adiposity. Notably, stratification for waist circumference quartiles revealed that the correlation between SUA and total hip BMD was significant (r = 0.444, p = 0.001) in the highest quartile (91–100 cm). Our results suggest that SUA might be beneficial for bone health in postmenopausal women being characterized by a more android fat distribution, ascribing to SUA a discriminant role during menopause transition, potentially relevant also for men.

scholarly journals The local concentration of Ca2+ correlates with BMP7 expression and osseointegration in patients with total hip arthroplasty

2020 ◽  
Author(s):  
Xiaodong Fu ◽  
Weili Wang ◽  
Xiaomiao Li ◽  
Yingjian Gao ◽  
Hao Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Femoral Head ◽  
Total Hip Arthroplasty ◽  
Hip Arthroplasty ◽  
Local Concentration ◽  
Mineral Density ◽  
Gruen Zone ◽  
Total Hip ◽  
Significant Difference ◽  
The Impact

Abstract Background: A successful osseointegration of total hip arthroplasty (THA) relies on the interplay of implant surface and bone marrow microenvironment. This study was undertaken to investigate the impact of perioperative biochemical molecules (Ca2+, Mg2+, Zn2+, VD, PTH) on the bone marrow osteogenetic factors (BMP2, BMP7, Stro-1+ cells) in the metaphyseal region of the femoral head, and further on the bone mineral density (BMD) of Gruen R3. Methods: Bone marrow aspirates were obtained from the discarded metaphysis region of the femoral head in 51 patients with THA. Flow cytometry was used to measure the Stro-1+ expressing cells. ELISA was used to measure the concentrations of bone morphologic proteins (BMP2 and BMP7). The perioperative concentrations of the biochemical molecules above were measured by radioimmunoassay. The BMD of Gruen zone R3 was examined at 6 months after THA, using dual-energy X-ray absorptiometry (DEXA).Results: Our data demonstrated that the concentration of Ca2+ was positively correlated with BMP7 expression, and with the postoperative BMD of Gruen zone R3. However, the concentration of Mg2+ had little impact on the R3 BMD, although it was negatively correlated with the expression of BMP7. The data also suggested that the other biochemical molecules, such as Zn2+, VD, and PTH, were not significantly correlated with any bone marrow osteogenetic factors (BMP2, BMP7, Stro-1+ cells). The postoperative R3 BMD of patients of different gender and age had no significant difference.Conclusions: These results indicate the local concentration of Ca2+ may be an indicator for the prognosis of THA patients.

scholarly journals The association between bone mineral density and postoperative drainage volume following cruciate-substituting primary total knee arthroplasty: a cross-sectional study

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Yuthasak Peerakul ◽  
Jirapong Leeyaphan ◽  
Karn Rojjananukulpong
Keyword(s):  
Blood Loss ◽  
Primary Total Knee Arthroplasty ◽  
Cross Sectional Study ◽  
Postoperative Blood Loss ◽  
Mineral Density ◽  
Cross Sectional ◽  
Total Hip ◽  
Drainage Volume ◽  
Hip Bmd ◽  
Postoperative Drainage

Abstract Background The prevalence of osteoporosis in patients who undergo a primary total knee arthroplasty (TKA) is increasing. Low bone mineral density (BMD) is related to unfavorable outcomes following TKA such as migration of uncemented tibial components. Postoperative blood loss in TKA is an important complication. Non-modifying predicting factors for postoperative blood loss in patients undergoing primary TKA need further elucidation. Studies on the association between BMD and blood loss after TKA are limited. We aimed to demonstrate the relationship between BMD and postoperative drainage volume following primary TKA. Methods A cross-sectional study was conducted between January 2014 and August 2020. A total of 119 primary varus osteoarthritis knees with BMD results were included in the study. Patients with secondary causes of osteoporosis were excluded. Results The median postoperative drainage volume of participants in the normal total hip BMD group and the normal trochanter BMD group was higher than that of patients in the low total hip BMD group and the low trochanter BMD group (285.0 ml vs 230.0 ml, P = 0.003; 282.5 ml vs 240.0 ml, P = 0.013, respectively). Multivariate regression analyses showed that operative time, spinal anesthesia, and normal total hip BMD status were significant predictive factors associated with increased postoperative drainage volume (P = 0.014, 0.022, and 0.013, respectively). No association was identified between the lumbar spine BMD status and postoperative drainage volume. Conclusions The relationship between BMD and postoperative blood loss in primary TKA was identified in this study. Normal total hip BMD was found to be associated with an increased postoperative drainage volume after primary TKA compared with low BMD.

scholarly journals Head-to-head comparisons of bisphosphonates and teriparatide in osteoporosis: a meta-analysis

2017 ◽  
pp. E146-E157 ◽  
Author(s):  
Chun-Lin Liu ◽  
Han-Chung Lee ◽  
Chun-Chung Chen ◽  
Der-Yang Cho
Keyword(s):  
Lumbar Spine ◽  
Femoral Neck ◽  
Treatment Effectiveness ◽  
Meta Analysis ◽  
Mineral Density ◽  
Total Hip ◽  
Nonvertebral Fractures ◽  
Post Menopausal Osteoporosis ◽  
Significant Difference ◽  
Post Menopausal

Purpose: This meta-analysis aimed to compare the efficacy and safety of teriparatide vs. bisphosphonates in the management of osteoporosis. Methods: A total of 1,967 patients from eight randomized controlled trials were analyzed; outcomes included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine, vertebral and nonvertebral fractures and any adverse event. A subgroup analysis of treatment effectiveness was performed according to the etiology of osteoporosis; i.e., glucocorticoid-induced osteoporosis (GIO) vs. post-menopausal osteoporosis (PO). Results: Teriparatide increased the BMD of the lumbar spine, femoral neck and total hip to a greater extent than bisphosphonates. Patients treated with teriparatide also had a lower risk of vertebral fractures compared with bisphosphonates; however, no difference in risk of nonvertebral fractures (or adverse events) was found. GIO subgroups showed larger increases in BMD of the lumbar spine, total hip and femoral neck in patients treated with teriparatide compared with bisphosphonates. The PO subgroup showed larger increases in BMD of the lumbar spine in patients treated with teriparatide compared with bisphosphonates. Patients in the GIO subgroup (but not the PO subgroup) were less likely to suffer a vertebral fracture on teriparatide as compared with bisphosphonates. In contrast, no significant difference in the percentage of nonvertebral fractures was noted between the two types of treatment for either subgroup. Conclusion: Teriparatide significantly increased the BMD of lumbar spine, total hip and femoral neck, particularly in GIO-induced osteoporosis. Teriparatide did not lower the risk of nonvertebral fractures when compared with bisphosphonates.

scholarly journals Effect of denosumab on trabecular bone score in de novo kidney transplant recipients

2019 ◽  
Vol 34 (10) ◽  
pp. 1773-1780 ◽  
Author(s):  
Marco Bonani ◽  
Diana Frey ◽  
Nicole Graf ◽  
Rudolf P Wüthrich
Keyword(s):  
Lumbar Spine ◽  
Trabecular Bone ◽  
Kidney Transplant ◽  
De Novo ◽  
Trabecular Bone Score ◽  
Distal Tibia ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mineral Density ◽  
Total Hip

Abstract Background Kidney transplant recipients (KTR) are at risk to lose bone mass. The trabecular bone score (TBS) represents a recently developed parameter of lumbar spine trabecular bone texture that correlates with the occurrence of fractures. Methods We analysed the 1-year changes in TBS in 44 de novo KTR that were randomized 1:1 to denosumab or no treatment. TBS was derived from dual energy X-ray absorptiometry and was correlated with 1-year areal bone mineral density (aBMD) changes at the lumbar spine and total hip. Correlations were also performed with parameters of peripheral bone microarchitecture and bone strength at the distal tibia and distal radius, as assessed by high-resolution peripheral quantitative computed tomography (HRpQCT) and micro-finite element analysis. Results The baseline TBS in KTR amounted to 1.312 ± 0.101, which is lower than the TBS of an age-matched normal control population (range 1.364–1.471). The TBS correlated positively with aBMD at the lumbar spine (Spearman’s ρ = 0.56; P < 0.001) and total hip (ρ = 0.33; P < 0.05). The baseline TBS also correlated with HRpQCT-derived total (ρ = 0.49; P < 0.05) and trabecular volumetric BMD (ρ = 0.57; P < 0.01) and trabecular separation (ρ = −0.46; P < 0.05) at the tibia. Denosumab treatment led to an increase in TBS, paralleling the BMD changes at the lumbar spine. Conclusions The TBS is a useful additional score of bone health, which may help to better define fracture risk. Treatment with denosumab led to improved trabecular bone texture in de novo KTR in addition to its beneficial effect on BMD.

scholarly journals Comparison of Teriparatide and Denosumab in Patients Switching From Long-Term Bisphosphonate Use

2019 ◽  
Vol 104 (11) ◽  
pp. 5611-5620 ◽  
Author(s):  
Houchen Lyu ◽  
Sizheng S Zhao ◽  
Kazuki Yoshida ◽  
Sara K Tedeschi ◽  
Chang Xu ◽  
...  
Keyword(s):  
Femoral Neck ◽  
The United States ◽  
First Year ◽  
Mineral Density ◽  
Total Hip ◽  
Academic Medical ◽  
Hip Bmd ◽  
Observational Cohort ◽  
Transient Loss

Abstract Context Teriparatide and denosumab are effective treatments for osteoporosis and typically reserved as second-line options after patients have used bisphosphonates. However, limited head-to-head comparative effectiveness data exist between teriparatide and denosumab. Objective We compared changes in bone mineral density (BMD) between groups treated with teriparatide or denosumab after using bisphosphonates, focusing on the change in BMD while on either drug over 2 years. Design Observational cohort study using electronic medical records from two academic medical centers in the United States. Participants The study population included osteoporotic patients >45 years who received bisphosphonates >1 year before switching to teriparatide or denosumab. Outcome Measures Annualized BMD change from baseline at the lumbar spine, total hip, and femoral neck. Results Patients treated with teriparatide (n = 110) were compared with those treated with denosumab (n = 105); the mean (SD) age was 70 (10) years and median duration (interquartile range) of bisphosphonate use was 7.0 (5.6 to 9.7) years. Compared with denosumab users, teriparatide users had higher annualized BMD change at the spine by 1.3% (95% CI 0.02, 2.7%) but lower at the total hip by −2.2% (95% CI −2.9 to −1.5%) and the femoral neck by −1.1% (95% CI −2.1 to −0.1%). Those who switched to teriparatide had a transient loss of hip BMD for the first year, with no overall increase in the total hip BMD over 2 years. Conclusions Among patients who use long-term bisphosphonates, the decision of switching to teriparatide should be made with caution, especially for patients at high risk of hip fracture.

scholarly journals Effect of once-daily fluticasone furoate/vilanterol versus vilanterol alone on bone mineral density in patients with COPD: a randomized, controlled trial

2020 ◽  
Vol 14 ◽  
pp. 175346662096514
Author(s):  
Francois Maltais ◽  
Isabelle Schenkenberger ◽  
Pascal L. M. L. Wielders ◽  
Juan Ortiz de Saracho ◽  
Kenneth Chinsky ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Mineral ◽  
Smoking History ◽  
Mineral Density ◽  
Fluticasone Furoate ◽  
Treatment Difference ◽  
Total Hip ◽  
Copd Exacerbations ◽  
Hip Bmd

Background: The relationship between inhaled corticosteroids and bone mineral density (BMD) remains uncertain despite extensive research. Methods: This was an international, multicenter, randomized, double-blind, parallel-group, 3-year noninferiority study. Patients with chronic obstructive pulmonary disease (COPD) (⩾40 years of age; smoking history ⩾10 pack years) and at least one native hip evaluable for BMD were enrolled and randomized 1:1, stratified by sex, to treatment with vilanterol (VI) 25 µg or fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg. BMD measurements were taken via dual-energy X-ray absorptiometry every 6 months. The primary endpoint was assessment of the noninferiority of change from baseline in total hip BMD per year at the −1% noninferiority level. Change from baseline in BMD at the lumbar spine and BMD measurements by sex were secondary endpoints. Incidences of COPD exacerbations and bone fractures throughout the study were also recorded. Results: Of 283 randomized patients, 170 (60%) completed the study. Noninferiority was demonstrated for FF/VI versus VI with regards to change from baseline in total hip BMD per year, with changes of −0.27% and 0.18%, respectively, and a treatment difference of −0.46% per year [95% confidence interval (CI) −0.97 to 0.06]. The treatment difference for FF/VI versus VI regarding lumbar spine BMD was −0.51% per year (95% CI −1.11 to 0.10). COPD exacerbations and bone fracture rates were similar between treatment groups. Conclusion: FF/VI showed noninferiority to VI for change from baseline in total hip BMD per year, when assessed at the −1% noninferiority margin in a combined sample of men and women with COPD. The reviews of this paper are available via the supplemental material section.

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