Postmenopausal Osteoporosis: Latest Guidelines Arceo-Mendoza, Rod Marianne; Camacho, Pauline M
Endocrinology and metabolism clinics of North America,
06/2021, Letnik:
50, Številka:
2
Journal Article
Recenzirano
Significant development has occurred in the treatment of postmenopausal osteoporosis. We review the most recent guidelines from the American Association of Clinical Endocrinologists/American College ...of Endocrinology, Endocrine Society, and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis/International Osteoporosis Foundation Guidelines.
The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of ...medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication.
Summary
Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures.
Introduction
The ...International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach.
Methods
Clinical perspective and updated literature search.
Results
The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis.
Conclusions
A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.
Abstract
Purpose
The efficacy and safety of abaloparatide, a parathyroid hormone-related protein analog for the treatment of osteoporosis in postmenopausal women at high fracture risk, is reviewed.
...Summary
A MEDLINE search was conducted for full text English-language articles, using the terms abaloparatide, parathyroid hormone, and osteoporosis. Published articles pertinent to the short- and long-term efficacy and safety of abaloparatide among postmenopausal women with osteoporosis were reviewed and summarized. Based on randomized, placebo-controlled and active-comparator studies, abaloparatide can reduce the risk of new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. Abaloparatide can also significantly increase bone mineral density (BMD) at the total hip, femoral neck, and lumbar spine. Patients receiving abaloparatide experience faster and more robust changes in BMD compared to those receiving teriparatide. Overall, abaloparatide is well tolerated with a mild adverse effect profile, including dizziness, headache, nausea, and palpitations. Additionally, there is a lower incidence of hypercalcemia with abaloparatide than with teriparatide. At this time, the differences demonstrated between abaloparatide and teriparatide would not be considered clinically significant. Larger and more robust studies are needed to determine future clinical significance of abaloparatide compared with other agents for use in the postmenopausal osteoporotic population.
Conclusion
Abaloparatide is an effective anabolic agent to improve bone formation and resorption amongst postmenopausal women with osteoporosis. Based on its clinical evidence, abaloparatide can result in greater BMD increases and less hypercalcemia compared with the only current marketed anabolic agent, teriparatide. Adverse events associated with abaloparatide are generally mild in nature and include nausea, dizziness, headache, and palpitations.
Abstract Background Postmenopausal osteoporosis results from bone loss and decreased bone strength mediated by an increased rate of bone remodeling secondary to reduced estrogen levels. Remodeling ...cycles are initiated by osteoclasts, the formation, function, and survival of which depend on RANK ligand (RANKL). RANKL inhibition therefore represents a novel strategy for reducing remodeling and its effects on fracture risk. Objectives The goal of this study was to review the preclinical and clinical evidence supporting the value of RANKL inhibition in conditions of bone loss and to provide the rationale for the use of the fully human antibody denosumab, a RANKL inhibitor, in such conditions. Methods We searched PubMed from January 2005 to May 2011 using the following terms: RANK Ligand , RANKL , denosumab , and NOT cancer, metastatic bone, or rheumatoid in the title. Results The search method retrieved 111 articles. Preclinical evidence from several bone disease models suggests that RANKL inhibition leads to increased bone volume, density, and strength. Denosumab prevents RANKL from binding to its receptor, decreasing osteoclast activity and thereby reducing bone resorption and increasing cortical and trabecular bone mass and strength. It has consistently been reported to reduce bone turnover, increase bone density, and reduce the risk of fracture in clinical studies of postmenopausal women. Phase III head-to-head trials comparing denosumab with the bisphosphonate alendronate reported that denosumab was associated with significantly greater increases in bone density. Eczema as an adverse event and cellulitis as a serious adverse event were more common with denosumab than with placebo. Conclusions Preclinical studies defined the role of RANKL in bone remodeling and provided evidence for the therapeutic potential of RANKL inhibition in conditions of bone loss. Clinical studies evaluating RANKL inhibition with denosumab in postmenopausal women have reported significant reductions in vertebral, nonvertebral, and hip fractures, providing evidence compatible with the use of denosumab in postmenopausal women with osteoporosis.
Objectives: The aim of this study is to define the frequency of vitamin D deficiency in postmenopausal women and to evaluate its implications on bone metabolism. Patients, who admitted to the Ankara ...University Faculty of Medicine Outpatient Clinics included to the study. Materials and Methods: The study was conducted as a cross-sectional study. Postmenopausal women were scanned with DEXA and divided into three groups as osteoporosis, osteopenia, and the control group according to the T scores. During medical visit, patients’ clothing habits, and daily sunlight exposure rates have been scored from 1 to 4 with a questionnaire. Vitamin D, Parathyroid hormone (PTH), osteocalcin, Dependent personality disorder (DPD), calcium, phosphorus, Alkaline phosphotase (ALP) levels were compared. Results: 29.8% of the women had osteoporosis, and 45.8% had osteopenia. Forty eight women (36.6%) were reported to have severe vitamin D deficiency (25-OH-D<10 ng/mL), 38 women (%29) moderate vitamin D deficiency (10≤25-OH-D<20 ng/mL), and 22 women (%16.8) mild vitamin D deficiency (20≤25-OH-D<30 ng/mL). Only 23 of the women (17.6%) had vitamin D levels higher than 30 ng/mL. It was observed that as the vitamin D levels dropped, PTH levels increased. The threshold for 25-OH-D level was estimated as 16.3 ng/mL. A negative relation was observed between vitamin D and osteocalcin and a positive relation was observed between ALP, osteocalcin and PTH. Conclusion: Since the research to find out preventive effects of vitamin D on chronic diseases such as cancer, hypertension, diabetes mellitus and it is already known that vitamin D reduces the risk of falls and fracture, closer follow-up of patients with vitamin D levels below 16.3 ng/mL with appropriate vitamin replacement may be important in reducing bone loss.
This review updates evidence since the 2002 U.S. Preventive Services Task Force recommendation on osteoporosis screening.
To determine the effectiveness and harms of osteoporosis screening in ...reducing fractures for men and postmenopausal women without known previous fractures; the performance of risk-assessment instruments and bone measurement tests in identifying persons with osteoporosis; optimal screening intervals; and the efficacy and harms of medications to reduce primary fractures.
Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2009), MEDLINE (January 2001 to December 2009), reference lists, and Web of Science.
Randomized, controlled trials of screening or medications with fracture outcomes published in English; performance studies of validated risk-assessment instruments; and systematic reviews and population-based studies of bone measurement tests or medication harms.
Data on patient populations, study design, analysis, follow-up, and results were abstracted, and study quality was rated by using established criteria.
Risk-assessment instruments are modest predictors of low bone density (area under the curve, 0.13 to 0.87; 14 instruments) and fractures (area under the curve, 0.48 to 0.89; 11 instruments); simple and complex instruments perform similarly. Dual-energy x-ray absorptiometry predicts fractures similarly for men and women; calcaneal quantitative ultrasonography also predicts fractures, but correlation with dual-energy x-ray absorptiometry is low. For postmenopausal women, bisphosphonates, parathyroid hormone, raloxifene, and estrogen reduce primary vertebral fractures. Trials are lacking for men. Bisphosphonates are not consistently associated with serious adverse events; raloxifene and estrogen increase thromboembolic events; and estrogen causes additional adverse events.
Trials of screening with fracture outcomes, screening intervals, and medications to reduce primary fractures, particularly those enrolling men, are lacking.
Although methods to identify risk for osteoporotic fractures are available and medications to reduce fractures are effective, no trials directly evaluate screening effectiveness, harms, and intervals.
Agency for Healthcare Research and Quality.
A guidance on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis was recently published in Osteoporosis International as a joint effort of the ...International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (Kanis et al. in Osteoporos Int
https://doi.org/10.1007/s00198-018-4704-5
, 2018). This manuscript updates the previous guidelines document, published in 2013 (Kanis et al. in Osteoporos Int 24:23–57, 2013) and is written in a European perspective. The present article reports and summarizes the main recommendations included in this 2018 guidance document.
What is the frequency of, and predictors for, osteoporosis, fractures, and osteoporosis management (investigation, treatment) in women with premature ovarian insufficiency (POI; menopause <40 years) ...and early menopause (EM; menopause 40-44years)?
Over the 23-year follow-up duration, at a mean age of 68 years, women with POI/EM had higher osteoporosis/fracture risk and prevalence, higher osteoporosis screening and anti-osteoporosis medication use compared to women with usual age menopause; increasing age was predictive of increased risk of osteoporosis/fracture and menopause hormone therapy (MHT) prior to or at study entry (aged 45-50 years) was protective.
Women with POI/EM have increased risk of osteoporosis and fractures with limited data regarding risk factors for reduced bone density and fractures. Clinical guidelines recommend screening with dual X-ray absorptiometry (DXA) and treatment with MHT for most women with POI/EM to reduce osteoporosis and fracture risk; however, studies indicate gaps in osteoporosis knowledge, guideline uptake, and management adherence by clinicians and women.
The Australian Longitudinal Study on Women's Health is a prospective longitudinal study of Australian women. This study uses the cohort of women born between 1946 and 1951, surveyed nine times between 1996 and 2019. Data from the Australian administrative health records, including hospital admissions data (fractures, osteoporosis), Medicare Benefits Schedule (DXA), and the Pharmaceutical Benefits Scheme (PBS; MHT, anti-osteoporosis medication, available only from 2002) were linked to survey data.
Survey respondents with self-reported age of menopause were included. POI/EM was defined as menopause <45 years. T-test or chi-square were used for comparisons at baseline (P < 0.05 indicates significance). Generalized estimating equations for panel data explored predictors for the longitudinal outcomes of osteoporosis, fractures, DXA rates, MHT use, and anti-osteoporosis medication (in women with osteoporosis/fracture, from Survey 4 onwards only). Univariable regression was performed, and variables retained where P < 0.2, to form the multivariable model, and bootstrapping with 100 repetitions at 95% sampling of the original dataset to ensure robustness of results.
Eight thousand six hundred and three women were included: 610 (7.1%) with POI/EM. Mean (SD) baseline age was 47.6 (1.45) years in the entire cohort and mean (SD) age of menopause was 38.2 (7.95) and 51.3 (3.04) years in women with POI/EM and usual age menopause, respectively (P < 0.001). Over the 23 years, of women with POI/EM, 303 (49.7%) had osteoporosis/fractures, 421 (69.0%) had DXA screening, 474 ever used MHT (77.7%), and 116 (39.1%) of those with osteoporosis/fractures used anti-osteoporosis medication. Of women with usual age menopause, 2929 (36.6%) had osteoporosis/fractures, 4920 (61.6%) had DXA screening, 4014 (50.2%) used MHT, and 964 (33.0%) of those with osteoporosis/fractures used anti-osteoporosis medication. Compared to women with menopause at age ≥45 years and after adjusting for other risk factors, women with POI/EM had increased risk of osteoporosis (odds ratio OR 1.37; 95% CI 1.07-1.77), fractures (OR 1.45; 1.15-1.81), DXA testing (OR 1.64; 1.42-1.90), MHT use (OR 6.87; 5.68-8.30), and anti-osteoporosis medication use (OR 1.50; 1.14-1.98). In women with POI/EM women, increasing age was associated with greater risk of osteoporosis/fracture (OR 1.09; 1.08-1.11), and MHT prior to or at study entry (aged 45-50 years), was protective (OR 0.65, 0.45-0.96). In women with POI/EM, age (OR 1.11; 1.10-1.12), fractures (OR 1.80, 1.38-2.34), current smoking (OR 0.60; 0.43-0.86), and inner (OR 0.68; 0.53-0.88) or outer regional (OR 0.63; 0.46-0.87) residential location were associated with DXA screening. In women with POI/EM, increasing age (OR 1.02; 1.01-1.02), and currently consuming alcohol (OR 1.17; 1.06-1.28), was associated with having ever used MHT. In the 299 women with POI/EM and osteoporosis/fractures, only 39.1% ever received treatment with an anti-osteoporosis medication. Increasing age (OR 1.07; 1.04-1.09) and lower BMI (OR 0.95; 0.92-0.98) were associated with greater likelihood of treatment with anti-osteoporosis medication.
Survey data including age of menopause were self-reported by participants; fracture questions were not included in the 2001 survey, and location or level of trauma of self-reported fractures was not asked. Additional risk/protective factors such as vitamin D status, calcium intake, and exercise were not able to be included. Due to sample size, POI and EM were combined for all analyses, and we were unable to differentiate between causes of POI/EM. PBS data were only available from 2004, and hospital admissions data were state-based, with all of Australia were only available from 2007.
This study supports previous literature indicating increased risk of osteoporosis and fractures in women with POI, and adds evidence for women with POI/EM, where there was a relative paucity of data. This is the first study to analyse a variety of clinical and demographic risk factors for osteoporosis and fractures in women with POI/EM, as well as analysing investigation and treatment rates. In these women, using MHT prior to or at study entry, aged 45-50 years, was protective for osteoporosis/fractures; however, having ever used MHT was not, highlighting the importance of early treatment with MHT in these women to preserve bone strength. Although women with POI/EM and osteoporosis or fractures were more likely to use anti-osteoporosis medications than those with usual age menopause, overall treatment rates are low at <40%, demonstrating a significant treatment gap that should be addressed to reduce future fracture risk.
This study was funded by The Australian NHMRC Centre of Research Excellence Women's Health in Reproductive Life (CRE-WHIRL, project number APP1171592). A.R.J. is the recipient of a National Health and Medical Research Council post-graduate research scholarship (grant number 1169192). P.R.E. is supported by a National Health and Medical Research Council grant 1197958. P.R.E. reports grants paid to their institution from Amgen, Sanofi, and Alexion, honoraria from Amgen paid to their institution, and honoraria from Alexion and Kyowa-Kirin.
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Administration of glucocorticoids is an effective strategy for treating many inflammatory and autoimmune diseases. However, glucocorticoid treatment can have adverse effects on bone, leading to ...glucocorticoid‐induced osteoporosis (GIO), the most common form of secondary osteoporosis. Although the pathogenesis of GIO has been studied for decades, over the past ten years the autophagy machinery has been implicated as a novel mechanism. Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO.
Although the pathogenesis of glucocorticoid‐induced osteoporosis (GIO) has been studied for decades, over the past ten years the autophagy machinery has been implicated as a novel mechanism. Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO.
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