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In this article, the American College of Physicians updates its 2017 recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. These updated guidelines examine new evidence comparing therapies among all at-risk populations, including men. Description: This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. Methods: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Audience and Patient Population: The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. Recommendation 1a: ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). Recommendation 1b: ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). Recommendation 2a: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). Recommendation 2b: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). Recommendation 3: ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). Recommendation 4: ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence). [ABSTRACT FROM AUTHOR]