This is the first update for 5 years since the previous guidance was published in 2017.
It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.
However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”
She also queries some of the other recommendations in the guidance.
Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.
Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
Systematic review
The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.
The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:
- Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
- Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
- Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).
The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
Major changes from 2017 guidelines, some questions
“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.
“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.
“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.
The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.
The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.
Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.
In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.
It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.
“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.
The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.