The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and ...adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs).
Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols.
The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options.
This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis.
= 25-hydroxyvitamin D;
= American Association of Clinical Endocrinologists;
= American College of Endocrinology;
= atypical femoral fracture;
= American Society for Bone and Mineral Research;
= best evidence level;
= bone mineral density;
= bone turnover marker;
= confidence interval;
= clinical practice guideline;
= C-terminal telopeptide type-I collagen;
= dual-energy X-ray absorptiometry;
= evidence level;
= U.S. Food and Drug Administration;
= Fracture Risk Assessment Tool;
= gastrointestinal;
= Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly Pivotal Fracture Trial (zoledronic acid and zoledronate are equivalent terms);
= International Society for Clinical Densitometry;
= international units;
= intravenous;
= least significant change;
= National Osteoporosis Foundation;
= osteonecrosis of the jaw;
= serum amino-terminal propeptide of type-I collagen;
= parathyroid hormone;
= recommendation;
= region of interest;
= relative risk;
= standard deviation;
= trabecular bone score;
= vertebral fracture assessment;
= World Health Organization.
Summary
An analysis of United States (US) Medicare claims data from 2002 to 2015 for women aged ≥ 65 years found that age-adjusted hip fracture rates for 2013, 2014, and 2015 were higher than ...projected, resulting in an estimated increase of more than 11,000 hip fractures.
Introduction
Hip fractures are a major public health concern due to high morbidity, mortality, and healthcare expenses. Previous studies have reported a decrease in the annual incidence of hip fractures in the US beginning in 1995, coincident with the introduction of modern diagnostic tools and therapeutic agents for osteoporosis. In recent years, there has been less bone density testing and fewer prescriptions for osteoporosis treatments. The large osteoporosis treatment gap raises concern of possible adverse effects on hip fracture rates.
Methods
We assessed hip fracture incidence in the US to determine if the previous decline in hip fracture incidence continued. Using 2002 to 2015 Medicare Part A and Part B claims for women ≥ 65 years old, we calculated age-adjusted hip fracture rates, weighting to the 2014 population.
Results
We found that hip fracture rates declined each year from 2002 to 2012 and then plateaued at levels higher than projected for years 2013, 2014, and 2015.
Conclusions
The plateau in age-adjusted hip fracture incidence rate resulted in more than 11,000 additional estimated hip fractures over the time periods 2013, 2014, and 2015. We recommend further study to assess all factors contributing to this remarkable change in hip fracture rate and to develop strategies to reduce the osteoporosis treatment gap.
Sclerostin is a small protein expressed by the SOST gene in osteocytes, bone cells that respond to mechanical stress applied to the skeleton and appear to play an important role in the regulation of ...bone remodeling. When sclerostin binds to its receptors on the cell surface of osteoblasts, a downstream cascade of intracellular signaling is initiated, with the ultimate effect of inhibiting osteoblastic bone formation. Recent studies have shown that the SOST gene is also expressed by articular chondrocytes and that modulation of its activity may have effects on articular cartilage and subchondral bone. The role of sclerostin in the pathogenesis of osteoarthritis in humans has not yet been defined, and the potential utility of treating osteoarthritis with interventions that alter sclerostin is not known. Rare genetic skeletal disorders in humans with low sclerostin levels, such as sclerosteosis and van Buchem disease, have been associated with a high bone mineral density (BMD) phenotype and low risk of fractures. This has led to the concept that antisclerostin interventions might be useful in the treatment of patients with osteoporosis and skeletal disorders associated with low bone mass. Compounds that inhibit sclerostin have been shown to stimulate bone formation and reduce bone resorption, with a robust increase in BMD. Investigational monoclonal antibodies to sclerostin, including romosozumab, blosozumab, and BPS804, have advanced to phase II clinical trials or beyond. If antisclerostin therapy is found to have beneficial effects on clinical endpoints, such as reduction of fracture risk or improvement in quality of life in patients with osteoarthritis, with a favorable balance of benefit and risk, then this class of compounds may become a prominent addition to the options for therapy of osteoporosis and other skeletal disorders.
Romosozumab binds sclerostin, increases bone formation, and decreases bone resorption. Postmenopausal women with osteoporosis were assigned to romosozumab or placebo for 1 year, followed by 1 year of ...denosumab. Romosozumab was associated with lower vertebral and clinical fracture risk.
Osteoporosis can lead to fragility fractures, which result in clinical burden and increased mortality.
1
,
2
Even after a fracture, fewer than 25% of patients receive pharmacologic treatment for osteoporosis.
3
–
5
After the discovery that sclerostin deficiency causes rare genetic conditions that are characterized by high bone mass and resistance to fracture,
6
,
7
sclerostin became a therapeutic target for the treatment of osteoporosis. Sclerostin, a negative regulator of bone formation that is secreted by osteocytes,
8
inhibits Wnt signaling, down-regulating this stimulus for osteoblast development and function.
9
Romosozumab (Amgen and UCB Pharma) is a monoclonal antibody that binds and inhibits sclerostin, with . . .
Abstract The amino-bisphosphonates are first-line therapy for the treatment of most patients with osteoporosis, with proven efficacy to reduce fracture risk at the spine, hip, and other nonvertebral ...skeletal sites. Further, bisphosphonates have been associated with a significant decrease in morbidity and increase in survival. Following the use of bisphosphonates in millions of patients in clinical practice, some unexpected possible adverse effects have been reported, including osteonecrosis of the jaw, atypical femur fractures, atrial fibrillation, and esophageal cancer. Because bisphosphonates are incorporated into the skeleton and continue to exert an antiresorptive effect for a period of time after dosing is discontinued, the concept of a drug holiday has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from antifracture efficacy. Patients receiving bisphosphonates who are not at high risk for fracture are potential candidates for a drug holiday, while for those with bone mineral density in the osteoporosis range or previous history of fragility fracture, the benefits of continuing therapy probably far outweigh the risk of harm.
Summary
Bone Health TeleECHO Moscow is the first Russian-speaking Project ECHO (Extension for Community Healthcare Outcomes) program that is modeled after the original Bone Health TeleECHO created in ...the USA. Bone Health TeleECHO Moscow was effective (effect size of 0.87 p < 0.001) at improving clinicians' skills in the management of osteoporosis based on self-evaluation over 3 years.
Introduction
Bone Health TeleECHO (Extension for Community Healthcare Outcomes) Moscow is the first Russian-speaking ECHO program, modeled after Bone Health TeleECHO at the University of New Mexico, USA. The bone ECHO programs are designed to expand the capacity to deliver best practice skeletal healthcare worldwide through ongoing technology-enabled case-based collaborative learning. To evaluate the impact of the first 3 years of Bone Health TeleECHO Moscow on physicians’ knowledge in the management of bone diseases.
Methods
Demographic data were obtained, and outcomes were assessed through an electronic blinded self-efficacy questionnaire focusing on competence and skills in 20 domains of osteoporosis care before and after each year of participation in the Bone Health TeleECHO Moscow.
Results
Over 3 years, a total of 296 participants completed the questionnaire. Average attendance for each monthly session increased from 64 in 2019 to 73 in 2020 and to 96 in 2021. Participants were from all regions of Russia and Russian-speaking countries. The mean age of respondents was 43 years with the youngest being 23 and the eldest 74. The most common participants’ primary specialties were endocrinology (
n
= 263), gynecology (
n
= 20), orthopedics (
n
= 3), and other (
n
= 10). All of our participants were physicians, including 73 MD PhDs. This educational intervention was associated with a statistically significant improvement in each of the 20 domains of osteoporosis care, with an effect size of 0.87 (
p
< 0.001).
Conclusion
Bone Health TeleECHO is effective at improving clinicians’ skills in the management of osteoporosis based on self-evaluation over 3 years.
The Pathophysiology and Treatment of Osteoporosis Drake, Matthew T., MD, PhD; Clarke, Bart L., MD; Lewiecki, E. Michael, MD, FACP, FACE
Clinical therapeutics,
08/2015, Letnik:
37, Številka:
8
Journal Article
Recenzirano
Abstract Purpose The objectives of this article are to review the pathophysiology of bone loss associated with aging and to review current pharmacologic approaches for the treatment of osteoporosis. ...Methods A literature search with PubMed was performed with the terms osteoporosis and pathophysiology and osteoporosis and treatment and limited to studies written in English that were published within the preceding 10 years. Given the large number of studies identified, we selectively reviewed those studies that contained primary data related to osteoporosis pathophysiology or osteoporosis pharmacologic treatments and references included within selected studies identified from abstract review. Findings Published studies have consistently reported that osteoporosis in older adults is caused by an imbalance of bone resorption in excess of bone formation. The dominant factor leading to bone loss in older adults appears to be gonadal sex steroid deficiency, with multiple genetic and biochemical factors, such as vitamin D deficiency or hyperparathyroidism, that may accelerate bone loss. Conditions that adversely affect growth and development may limit development of peak bone mass and accelerate subsequent bone loss. Studies of bone microarchitecture have shown that trabecular bone loss begins in the third decade of life, before gonadal sex steroid deficiency develops, whereas cortical loss typically begins in the sixth decade, about the time of menopause in women and about the same age in men. Antiresorptive agents for the treatment of osteoporosis act primarily by limiting osteoclast activity, whereas osteoanabolic agents, such as teriparatide, act primarily by stimulating osteoblastic bone formation. Clinical investigation of new compounds for the treatment of osteoporosis is mainly directed to those that stimulate bone formation or differentially decrease bone resorption more than bone formation. Therapies for osteoporosis are associated with adverse effects, but in patients at high risk of fracture, the benefits generally far outweigh the risks. Implications Current osteoporosis therapies mitigate or reverse the loss of bone associated with age-related decreases of gonadal sex steroids, increase bone strength, and reduce fracture risk. With improved knowledge of the pathophysiology of osteoporosis, new targets for therapeutic intervention have been identified. Clinical investigations of potential new treatments for osteoporosis are primarily directed to stimulating osteoblastic bone formation or to modulating the balance of bone resorption and formation in ways that improve bone strength.
Globally, one in five men aged >50 years is predicted to experience an osteoporotic fracture. Because of the treatment gap in osteoporosis and the paucity of bone-forming agents for men, new ...osteoporosis treatments are needed.
To evaluate the safety and efficacy of romosozumab in men with osteoporosis.
Phase III randomized BRIDGE study (placebo-controlled double-blind study evaluating the efficacy and safety of romosozumab in treating men with osteoporosis; ClinicalTrials.gov identifier, NCT02186171) for 12 months.
Thirty-one centers in Europe, Latin America, Japan, and North America.
Men aged 55 to 90 years with a baseline bone mineral density (BMD) T-score at the lumbar spine (LS), total hip (TH), or femoral neck of ≤-2.5 or ≤-1.5 with a history of a fragility nonvertebral or vertebral fracture.
The subjects were randomized 2:1 to receive romosozumab 210 mg subcutaneously monthly or placebo for 12 months.
The primary efficacy endpoint was percentage change from baseline in LS BMD at month 12.
In 245 subjects (163 romosozumab, 82 placebo), at month 12, the mean percentage change from baseline in the LS and TH BMD was significantly greater for the romosozumab group than for the placebo group (LS, 12.1% vs 1.2%; TH, 2.5% vs -0.5%; P < 0.001). Adverse events and serious adverse events were balanced between the two groups, with a numerical imbalance in the positively adjudicated cardiovascular serious adverse events romosozumab, 8 (4.9%) vs placebo, 2 (2.5%).
Treatment with romosozumab for 12 months increased the spine and hip BMD compared with placebo and was well tolerated in men with osteoporosis.
Denosumab for the treatment of osteoporosis Zaheer, Sarah; LeBoff, Meryl; Lewiecki, E Michael
Expert opinion on drug metabolism & toxicology,
03/2015, Letnik:
11, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Introduction: Low trauma fractures due to osteoporosis are a major health concern worldwide. Despite the availability of many therapeutic compounds to reduce fracture risk, osteoporosis remains ...undertreated and the burden of osteoporotic fractures remains high. Denosumab is a novel agent that acts to reduce bone turnover, improve bone mineral density, and reduce fracture risk, offering a favorable efficacy and safety profile.Areas covered: This review covers the pharmacology and major clinical trials with extension/post-marketing follow-up, including trials for all FDA-approved indications of denosumab to date.Expert opinion: Denosumab is an efficacious and safe osteoporosis treatment option, with current data from up to 8 years of continued use showing continued improvement in bone density with sustained fracture risk reduction. Safety profiles overall are similar to placebo, with no new safety concerns in extension trials, though a theoretical increased risk of infection exists with RANKL inhibition. Future considerations include safety of prolonged treatment beyond 8 years, and efficacy/fracture risk after discontinuation or with non-adherence, given the characteristic pharmacodynamic profile of denosumab.
Postmenopausal osteoporosis is a disease of high bone remodeling, with an imbalance of bone resorption over bone formation, resulting in decreased bone mineral density and disruption of bone ...microarchitecture. With our improved understanding of the molecular and cellular regulators and mediators of bone remodeling, new targets for therapeutic intervention have been identified. Receptor activator of nuclear factor κB ligand (RANKL) is the principal regulator of osteoclast differentiation, activity, and survival; denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and is approved for the treatment of women with postmenopausal osteoporosis at high risk of fractures. Cathepsin K is a protease produced by activated osteoclasts that degrades the protein matrix of bone. An inhibitor of cathepsin K, odanacatib, is in phase III clinical trials for the treatment of postmenopausal osteoporosis; it decreases bone resorption while seeming to suppress bone formation less than other antiresorptive agents. Sclerostin is a cytokine produced by osteocytes that inhibits osteoblastic bone formation; investigational monoclonal antibodies to sclerostin, such as AMG 785, have osteoanabolic properties with the potential to improve clinical outcomes in patients with osteoporosis. These and other novel interventions that target newly recognized regulators of bone remodeling are promising agents for the treatment of osteoporosis.
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