Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline from the American College of Physicians
Primary osteoporosis ( osteoporosis that is not secondary to a separate condition or medication) is characterized by a decrease in bone mass and density and a reduction in bone strength leading to an increased risk of fracture. Fractures can occur in any bone, but hip and spine fractures are the most common, accounting for 42% of all osteoporotic fractures. Fractures are associated with serious morbidity and mortality, and people with prevalent fractures have a much higher risk of future fractures (3–5). Overall, an estimated 10.2 million people age 50 and older in the United States have osteoporosis, and about 43.3 million people (>40% of U.S. older adults) have osteoporosis. low bone mass associated with a high risk of progression to osteoporosis.
This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacological treatment of primary osteoporosis or low bone mass to prevent fractures in adults.
The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of the evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.
The audience for this guideline includes all physicians. The patient population includes adults with primary osteoporosis or low bone mass.
Recommendation 1a: ACP recommends that physicians use bisphosphonates for initial drug treatment to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). Recommendation 1b: ACP suggests that physicians use bisphosphonates for initial drug treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). Recommendation 2a: The ACP suggests that physicians use the RANK ligand inhibitor (denosumab) as a second-line drug treatment to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis who have contraindications or experience adverse effects from bisphosphonates (conditional recommendation; evidence from moderate certainty). Recommendation 2b: The ACP suggests that physicians use the RANK ligand inhibitor (denosumab) as a second-line drug treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who have contraindications or experience adverse effects from bisphosphonates (conditional recommendation; evidence-certainty low) . Recommendation 3: The ACP suggests that doctors use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce fracture risk only in women with primary osteoporosis with very high risk of fracture (conditional recommendation). Recommendation 4: ACP suggests that clinicians take an individualized approach to whether to initiate drug treatment with a bisphosphonate in women over 65 years of age with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence). |
The American College of Physicians (ACP) has published an update to its guideline with clinical recommendations for treatments of primary osteoporosis and low bone mass in adults. In the new guideline, the ACP recommends bisphosphonates as initial pharmacological treatment to reduce the risk of fractures in men and postmenopausal women diagnosed with primary osteoporosis. The complete guideline is published in Annals of Internal Medicine .
Osteoporosis is a systemic skeletal disease characterized by decreased bone mass and deterioration of bone tissue leading to an increased risk of bone fragility and fracture, especially in the hip, spine and wrist. Overall, approximately 10.2 million people aged 50 years and older in the United States have osteoporosis, and about 43.3 million people (>40% of U.S. older adults) have associated low bone mass. with a high risk of progression to osteoporosis.
The guideline examines new evidence that has emerged on the effectiveness of human parathyroid hormone-related peptides, sclerostin inhibitors, the comparative effectiveness of treatments, and treatments in men. In postmenopausal women and men with primary osteoporosis, bisphosphonates had the most favorable balance of benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to the net clinical benefits, bisphosphonates are much cheaper than other drug treatments and are available in generic oral and injectable formulations.
Current evidence suggests that increasing the duration of bisphosphonate therapy beyond 3 to 5 years reduced the risk of new vertebral fractures, but not the risk of other fractures. However, there is a greater risk of long-term damage. Therefore, physicians should consider discontinuing bisphosphonates after five years of treatment, unless there is a strong indication to continue treatment.
The guideline also suggests that physicians use the RANK ligand inhibitor (denosumab) as a second-line drug treatment to reduce the risk of fractures in postmenopausal women and men diagnosed with primary osteoporosis who have contraindications or experience adverse effects from bisphosphonates.
ACP suggests that doctors use the sclerostin inhibitor (romosozumab) or recombinant PTH (teriparatide), followed by a bisphosphonate, to reduce fracture risk only in women with primary osteoporosis at very high fracture risk.
The guideline is based on a systemic review and network meta-analysis conducted by the ACP Center for Evidence Review at the Portland Veterans Affairs Research Foundation. The ACP Clinical Guidelines Committee plans to maintain this topic as a living guideline with literature monitoring and periodic updating of the systematic review and clinical recommendations.
Clinical considerations • Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle modifications, including exercise and counseling for fall assessment and prevention. • Adequate calcium and vitamin D intake should be part of fracture prevention in all adults with low bone mass or osteoporosis. • Clinicians should assess baseline fracture risk based on individualized assessment of bone density, fracture history, response to prior osteoporosis treatments, and multiple fracture risk factors. There are many risk assessment tools available with variable predictive value, which were not evaluated in the systematic review or this guideline. • Current evidence suggests that increasing the duration of bisphosphonate therapy beyond 3 to 5 years reduces the risk of new vertebral fractures but not the risk of other fractures. However, there is a greater risk of long-term damage. Therefore, physicians should consider discontinuing bisphosphonate treatment after 5 years, unless the patient has a strong indication to continue treatment. • The decision to temporarily discontinue bisphosphonate treatment (vacation) and its duration should be individualized and based on the initial risk of fractures, the type of medication and its bone half-life, benefits and harms (increased risk of fracture due to to drug suspension). • Women initially treated with an anabolic agent should be offered an antiresorptive agent after discontinuation to preserve gains and because of the serious risk of rebound and multiple vertebral fractures. • Older adults (eg, those over 65 years of age) with osteoporosis may be at increased risk for falls and other adverse events due to polypharmacy or drug interactions. Individualized treatment selection should address contraindications and precautions for medications indicated to treat osteoporosis based on comorbidities and concomitant medications, as well as reassessment of other medications associated with an increased risk of falls and fractures. • There is a variable risk of low bone mass in transgender people depending on age at gonadectomy, sex hormone therapy, distribution of comorbidities, and behavioral risk factors for osteoporosis and fractures. When considering potential fracture risk, history of gonadectomy (including age) and sex steroid therapy should be considered in treatment decisions for secondary osteoporosis. |
