Clinical Guidelines for Family Physicians

Treatment of low bone density or osteoporosis to prevent fractures in men and women


Osteoporosis is defined by a clinically diagnosed fragility fracture or a bone mineral density (BMD) of at least 2.5 SD below the mean for young female adults, usually measured by dual-energy x-ray absorptiometry. Risk factors include age, female sex, post-menopause, hypogonadism or premature ovarian failure, history of cigarette smoking or alcohol consumption (3 or more drinks daily), rheumatoid arthritis, or medications including glucocorticoids, anticoagulants, anticonvulsants, and aromatase inhibitors.

This guideline update focuses on treatment with bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) and denosumab. Denosumab, a human monoclonal antibody against RANK-ligand, approved by the Food and Drug Administration for treatment of osteoporosis, has been added to the list of allowed medications since publication of the 2008 guideline. Several therapies have been excluded from the update, including calcitonin, which is no longer widely used for osteoporosis treatment, and etidronate and pamidronate, neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis. It should be noted that the evidence continues to be insufficient regarding the effectiveness of therapies to prevent fractures or to treat osteoporosis in men.

Dr. Neil Skolnik, professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health

Dr. Neil Skolnik

Recommendation: Pharmacologic treatment is recommended using alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women who have known osteoporosis diagnosed as a T score less than –2.5 or those with fragility fracture (strong recommendation with high-quality evidence). Bisphosphonates, denosumab, teriparatide, and/or raloxifene reduce vertebral fractures. Alendronate, risedronate, zoledronic acid, and denosumab reduce both nonvertebral fractures and hip fractures. Moderate-quality evidence from one study that detected fractures radiographically showed that zoledronic acid reduced vertebral fractures in osteoporotic men. Moderate-quality evidence showed that alendronate, risedronate, and teriparatide reduced fracture risk in patients taking glucocorticoids. High-quality evidence showed that bisphosphonates are at least as effective for older patients as they are for younger patients. Evidence is insufficient to determine the comparative effectiveness of pharmacologic therapy or the superiority of one medication over another, within the same class or among classes, for prevention of fractures.

Bisphosphonates are associated with mild upper GI symptoms, atypical subtrochanteric fracture, and rare osteonecrosis of the jaw. There is no significant association between bisphosphonate use and total cardiovascular adverse events. Evidence is insufficient to associate bisphosphonates with increased cancer risk. Zoledronic acid is associated with atrial fibrillation, arthritis/arthralgias, headaches, hypocalcemia, influenza-like symptoms, and an increased incidence of uveitis/episcleritis. Denosumab is associated with mild upper GI symptoms, rash/eczema, and cellulitis.

While in the past additional medications were recommended for osteoporosis, the current guidelines recommend against using raloxifene, ibandronate, teriparatide, menopausal estrogen therapy, or menopausal estrogen plus progesterone therapy for first-line pharmacologic treatment.

The overall effect of calcium, vitamin D, or exercise alone on fracture risk is uncertain. Calcium and vitamin D may be added to treatment regimens, as a majority of trials with bisphosphonate therapy added this supplementation. Dosages should be considered because excessive dosing has been associated with hypercalcemia. Although previous data suggested an association between calcium supplementation and increased risk for myocardial infarction, moderate-quality evidence shows no association, though there is a risk of kidney stones.

Recommendation: Women who have osteoporosis and receive pharmacologic treatment should be treated for 5 years (weak recommendation; low-quality evidence). The evidence to determine the length of treatment is not strong, so recommendation is an extrapolation from existing evidence. High-risk patients may benefit from more than 5 years of treatment. Data suggests that patients treated with alendronate who had preexisting fractures or those with a BMD of –2.5 or less after 5 years of initial therapy may benefit from continued treatment, because these patients experienced a decreased incidence of new clinical vertebral fractures.

Recommendation: Pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture can be offered to men who have clinically recognized osteoporosis (weak recommendation, low-quality evidence). No evidence suggests that outcomes associated with pharmacologic treatment would differ between men and women if based on similar BMDs.

Recommendation: Bone density monitoring is not recommended during the 5-year pharmacologic treatment period for osteoporosis in women (weak recommendation, low-quality evidence). Data showed that most women with normal dual-energy x-ray absorptiometry scores did not progress to osteoporosis within 15 years. Data also does not support monitoring BMD during the initial 5 years of treatment in patients taking pharmacologic agents to treat osteoporosis. Several studies showed that women treated with antiresorptive treatment benefited from reduced fractures with treatment even if BMD did not increase.

Only 10% of women with normal or mild osteopenia develop osteoporosis within 15 years; 10% of women with moderate osteopenia develop osteoporosis within 5 years, and 10% of women with advanced osteopenia develop osteoporosis within 1 year.

Recommendation: The decision about whether to treat osteopenic women older then 65 years of age who are at a high risk for fracture should be based on a discussion of with the patient about their risk of fracture and the risk and benefits of treatment. Clinicians can use their judgment regarding the qualitative risk for fracture, or a validated tool such as the FRAX tool that gives 10-year risk of any major osteoporotic fracture and of hip fracture. The FRAX site recommends consideration of treatment for individuals with low bone mass (T-score between –1.0 and –2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture of at least 3% or a 10-year probability of a major osteoporosis-related fracture greater than 20%.

Bottom line:

Clinicians should offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women who have known osteoporosis diagnosed as a T score less than –2.5 or those with a fragility fracture. Pharmacologic therapy should be used for 5 years; however, high risk patients may benefit from longer treatment. There is no benefit to bone density monitoring during the 5-year pharmacologic treatment period. In addition, bisphosphonates should be considered in men who have clinically recognized osteoporosis.


Qaseem, A, Forciea, MA, McLean RM, Denberg TD. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Int Med. 2017;166(11):818-39.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Meizinger is a second year resident in the Family Medicine Residency Program at Abington Jefferson Health.

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