scholarly journals Antifracture Efficacy of Antiresorptive Agents Are Related to Changes in Bone Density

2000 ◽  
Vol 85 (1) ◽  
pp. 231-236 ◽  
Author(s):  
Richard D. Wasnich ◽  
Paul D. Miller
Keyword(s):  
Fracture Risk ◽  
Conceptual Model ◽  
Bone Strength ◽  
Measurement Errors ◽  
Current Debate ◽  
Mineral Density ◽  
Short Term ◽  
Antiresorptive Agents ◽  
Antiresorptive Drugs

There is a current debate about the extent to which antifracture efficacy of antiresorptive drugs are related to changes in bone mineral density (BMD). In vitro studies show that most of the variability in bone strength is related to BMD, and prospective studies have shown that low BMD is an important predictor of fracture risk. It seems that higher levels of bone turnover are also associated with increased fracture risk. Over the short term, a reduction in activation frequency or resorption depth would lead to fewer (and/or shallower) resorption sites and refilling of existing sites initially. There is also evidence that inhibiting resorption allows bone to respond to mechanical demands, preferentially thickening critical trabeculae, and this may help compensate for reduced connectivity. Each of these mechanisms would increase BMD and would disproportionately improve bone strength. Over the long term, maintaining bone mass and preventing loss of structural elements would result in progressively greater differences in BMD and fracture risk over time, relative to untreated women. The conceptual model predicts that both the short- and long-term antifracture efficacy of antiresorptive drugs will depend on the extent to which treatment can increase and maintain BMD. To examine this issue, we compiled data from clinical trials of antiresorptive agents and plotted the relative risk of vertebral fractures against the average change in BMD for each trial. The confidence intervals are large for individual trials, and there was substantial variability in antifracture efficacy at any given level of change in BMD. Overall, however, trials that reported larger increases in BMD tended to observe greater reductions in vertebral fracture risk. Poisson regression was used to quantify this relationship. The model predicts that treatments that increase spine BMD by 8% would reduce risk by 54%; most of the total effect of treatment was explained by the 8% increase in BMD (41% risk reduction). These findings are consistent with the short-term predictions of the conceptual model and with reports from randomized trials. The small but significant reductions in risk that were not explained by measurable changes in BMD might be related to publication bias, measurement errors, or limitations of current BMD technology.

scholarly journals On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mehran Ashrafi ◽  
Farzan Ghalichi ◽  
Behnam Mirzakouchaki ◽  
Manuel Doblare
Keyword(s):  
Mathematical Model ◽  
Bone Density ◽  
Bone Remodeling ◽  
Dental Implants ◽  
Implant Design ◽  
Patient Specific ◽  
Dental Implantation ◽  
Antiresorptive Agents ◽  
Antiresorptive Drugs

AbstractBone remodeling identifies the process of permanent bone change with new bone formation and old bone resorption. Understanding this process is essential in many applications, such as optimizing the treatment of diseases like osteoporosis, maintaining bone density in long-term periods of disuse, or assessing the long-term evolution of the bone surrounding prostheses after implantation. A particular case of study is the bone remodeling process after dental implantation. Despite the overall success of this type of implants, the increasing life expectancy in developed countries has boosted the demand for dental implants in patients with osteoporosis. Although several studies demonstrate a high success rate of dental implants in osteoporotic patients, it is also known that the healing time and the failure rate increase, necessitating the adoption of pharmacological measures to improve bone quality in those patients. However, the general efficacy of these antiresorptive drugs for osteoporotic patients is still controversial, requiring more experimental and clinical studies. In this work, we investigate the effect of different doses of several drugs, used nowadays in osteoporotic patients, on the evolution of bone density after dental implantation. With this aim, we use a pharmacokinetic–pharmacodynamic (PK/PD) mathematical model that includes the effect of antiresorptive drugs on the RANK/RANK-L/OPG pathway, as well as the mechano-chemical coupling with external mechanical loads. This mechano-PK/PD model is then used to analyze the evolution of bone in normal and osteoporotic mandibles after dental implantation with different drug dosages. We show that using antiresorptive agents such as bisphosphonates or denosumab increases bone density and the associated mechanical properties, but at the same time, it also increases bone brittleness. We conclude that, despite the many limitations of these very complex models, the one presented here is capable of predicting qualitatively the evolution of some of the main biological and chemical variables associated with the process of bone remodeling in patients receiving drugs for osteoporosis, so it could be used to optimize dental implant design and coating for osteoporotic patients, as well as the drug dosage protocol for patient-specific treatments.

scholarly journals Skeletal Microstructure and Estimated Bone Strength Improve Following Parathyroidectomy in Primary Hyperparathyroidism

2017 ◽  
Vol 103 (1) ◽  
pp. 196-205 ◽  
Author(s):  
Natalie E Cusano ◽  
Mishaela R Rubin ◽  
Barbara C Silva ◽  
Yu-Kwang Donovan Tay ◽  
John M Williams ◽  
...  
Keyword(s):  
Finite Element Analysis ◽  
Finite Element ◽  
Bone Density ◽  
Primary Hyperparathyroidism ◽  
Fracture Risk ◽  
Bone Strength ◽  
Failure Load ◽  
Mineral Density ◽  
Element Analysis ◽  
Volumetric Bone Density

Abstract Context High-resolution peripheral quantitative computed tomography (HRpQCT) is a noninvasive imaging technology that can provide insight into skeletal microstructure and strength. In asymptomatic primary hyperparathyroidism (PHPT), HRpQCT imaging has demonstrated both decreased cortical and trabecular indices, consistent with evidence for increased fracture risk. There are limited data regarding changes in HRpQCT parameters postparathyroidectomy. Objective To evaluate changes in skeletal microstructure by HRpQCT in subjects with PHPT after parathyroidectomy. Design We studied 29 subjects with PHPT (21 women, 8 men) with HRpQCT at baseline and 6, 12, 18, and 24 months postparathyroidectomy. Main Outcome Measures Volumetric bone mineral density, microarchitectural indices, and finite element analysis at the distal radius and tibia. Results At both the radius and tibia, there were significant improvements in total, cortical, and trabecular volumetric bone density as early as 6 months postparathyroidectomy (24-month values for total volumetric bone density, radius: +2.8 ± 4%, tibia: +4.4 ± 4%; P < 0.0001 for both), cortical thickness (radius: +1.1 ± 2%, tibia: +2.0 ± 3%; P < 0.01 for both), and trabecular bone volume (radius: +3.8 ± 5%, tibia: +3.2 ± 4%; P < 0.0001 for both). At both sites, by finite element analysis, stiffness and failure load were improved starting at 6 months postparathyroidectomy (24-month values for failure load, radius: +6.2 ± 6%, tibia: +4.8 ± 7%; P < 0.0001 for both). Conclusions These results provide information about skeletal microarchitecture in subjects with PHPT followed through 2 years after parathyroidectomy. Estimated bone strength is improved, consistent with data showing decreased fracture risk postparathyroidectomy.

scholarly journals Bone Mineral Density and Fracture Risk in Obese Older Adults 12 Months After Completion of a 6-Month Higher Protein Diet and Exercise Intervention

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 67-67
Author(s):  
Kathryn Porter Starr ◽  
Michael Borack ◽  
Kenneth Lyles ◽  
Marshall Miller ◽  
Jamie Rincker ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Older Adults ◽  
Weight Loss ◽  
Body Weight ◽  
Fracture Risk ◽  
G Protein ◽  
Bone Mineral ◽  
Protein Diet ◽  
Mineral Density

Abstract Objectives Weight loss interventions for older adults often reduce bone mineral density (BMD), increasing risk of subsequent detrimental outcomes. This study explored the long-term impact of a higher protein diet plus exercise versus a diet plus exercise control treatment on body weight, bone mineral density at 3 sites, and fracture risk. Methods Obese (BMI 34.3 ± 4.7 kg/m2) older adults (n = 55; age = 70.0 ± 6.1 yrs) with Short Physical Performance Battery (SPPB) score = 9.2 ± 1.4 (out of 12) who completed a 6-month weight loss plus exercise trial were invited to return for assessment 12 months later. The original randomization was to either 0.8 g protein/kg body weight (Control) or 1.2 g protein/kg body weight, predominantly dairy (Protein). The 18-month assessment included BMD by DEXA (Hologic, Horizon model A) for femoral neck (FN), total hip (TH), and spine (lumbar vertebrae 1–4; LS), as well body weight and secondary outcomes for Fracture Risk Assessment Tool (FRAX). Results A total of 38 (69.1%) study completers were assessed at 18 mo. Body weight was lower than baseline for both Control and Protein (P < 0.01), with Control (−4.8%) trending towards better maintenance of weight loss vs Protein (−2.3%) (P = 0.06). BMD at 18 mo. was not different from baseline in both Control and Protein for LS (0.01 ± 0.05 g/cm2 and −0.0002 ± 0.05 g/cm2; P = 0.512), FN (−0.01 ± 0.07 g/cm2 and −.009 ± 0.04 g/cm2; P = 0.814) and TH (−0.012 ± 0.03 g/cm2 and −.008 ± 0.033 g/cm2; P = 0.685). Change in BMD at 18 mo. did not differ by group at any site; the previously reported Protein group increase in LS at 6 mo. was not sustained. For individual fracture risk, between 0 and 18 mo., 6 improved (5 osteopenia to normal, 1 osteoporosis to osteopenia) and 1 worsened (normal to osteopenia but FRAX score below total and hip fracture thresholds). Conclusions The finding that obese older adults can maintain a lower body weight for 12 months without a decline in BMD and no increase in fracture risk amplifies our previous findings of legacy benefits of a short term obesity intervention for older adults. Further study is needed to determine if the protein benefit to LS is sustained if the higher protein intake is continued long term. Funding Sources This study was funded by the National Dairy Council and the US Department of Veterans Affairs Rehabilitation Research and Development Program.

Contemporary analysis of bone mineral density in men initiating androgen deprivation therapy for prostate cancer.

2019 ◽  
Vol 37 (27_suppl) ◽  
pp. 38-38
Author(s):  
Jason Hu ◽  
Armen G. Aprikian ◽  
Marie Vanhuyse ◽  
Alice Dragomir
Keyword(s):  
Prostate Cancer ◽  
Bone Mineral Density ◽  
Fracture Risk ◽  
Androgen Deprivation Therapy ◽  
Bone Mineral ◽  
Androgen Deprivation ◽  
Rural Residence ◽  
Mineral Density ◽  
Bmd Testing

38 Background: Androgen deprivation therapy (ADT) is a cornerstone of advanced prostate cancer (PCa) treatment, however several side-effects are associated with its long-term use. Notably, loss of bone mineral density (BMD) is accelerated which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to properly assess baseline fracture risk. The objective was to examine the proportion of BMD testing in men initiating long-term ADT in Quebec. Methods: The cohort consists of men extracted from Quebec public healthcare insurance administrative databases who were diagnosed with PCa from 2001-2012 and treated by ADT for at least one continuous year. The primary study outcome was the receipt of baseline BMD testing (defined as a BMD test identified in the period from 6 months prior to and up to 12 months after ADT initiation). Multivariable generalized linear mixed with a logit link was performed to identify variables associated with baseline BMD testing accounting for physician clustering. Results: We identified 7,069 patients, of which 887 (12.6%) underwent baseline BMD testing. Baseline BMD testing varied by year of ADT initiation, from 7.7% in 2001-2003 to 12.3% in 2013-2012. Following multivariable analyses, later years of ADT initiation (2004-2006, 2007-2009, 2010-2012, 2013-2015) remained associated with higher odds of baseline BMD testing compared to the earlier years (2001-2003) (ORs ranging from 1.43-1.88; p < 0.001). Conversely, age > 80 (OR 0.73; 95% CI 0.57-0.94; p = 0.001), greater Charlson comorbidity score (OR 0.51; 95%CI 0.34-0.75; p = 0.001), and rural residence (OR 0.60; 95%CI 0.48-0.75; p < 0.001) were associated with lower odds of baseline BMD testing. Conclusions: In our study population, rates of baseline BMD testing in men initiating ADT are low, although the rates increased over the course of the study period. Potential gaps identified in baseline BMD testing include older, more comorbid patients, and rural residence. Additional efforts emphasizing the importance of BMD testing in PCa guidelines may be needed.

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