Osteoporosis Guidelines, an ACP Update 2017

The recent ACP update on osteoporosis guidelines is shown below. Interestingly, American College of Physicians recommends against the use of DEXA/bone scans for treatment surveillance; although evidence quality is low for such an advice. Recommendations are listed with slight modified wording for easier and succinct reading.

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Annals of Internal Medicine

Guidelines

May 2017

RECOMMENDATION 1: ACP recommends that clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. (Grade: strong recommendation; high-quality evidence)

High-quality evidence showed that pharmacologic treatment in postmenopausal women who have osteoporosis (T scores ≤ –2.5 or those who have experienced fragility fractures) is beneficial for preventing further bone loss and reducing the risk for initial or subsequent fractures. Some bisphosphonates (alendronate, risedronate, and zoledronic acid) and the newer biologic agent denosumab reduce radiographic vertebral as well as clinical, nonvertebral, and hip fractures.

Both bisphosphonates and denosumab are associated with mild gastrointestinal symptoms. Denosumab is also associated with increased risk for infection and rash or eczema. Bisphosphonates are associated with atypical subtrochanteric fractures and osteonecrosis of the jaw. Although there is no association between bisphosphonates and atrial fibrillation, some studies have reported increased cardiovascular events. Zoledronic acid is associated with hypocalcemia, influenza-like symptoms, arthritis and arthralgias, headache, and uveitis.

Although evidence showed that raloxifene and ibandronate reduce radiographic vertebral fractures, and teriparatide reduces vertebral and nonvertebral fractures, studies have shown no benefit for these drugs to reduce all fracture types; therefore, they are not recommended as a first-line pharmacologic treatment. Raloxifene is associated with serious harms, such as thromboembolism. Calcitonin, which is no longer widely used for osteoporosis treatment, was not considered in this guideline.

Calcium and vitamin D may be added as dietary supplements to osteoporosis treatment regimens, although the effectiveness of these regimens on fracture prevention is unclear. The majority of trials with bisphosphonate therapy gave women calcium supplements and many also gave vitamin D; therefore, supplementation with these agents may be considered. However, dosages should be carefully considered, because excess dosing has been associated with hypercalcemia. Moderate-quality evidence showed no association between calcium supplementation and increased risk for myocardial infarction, but a large trial demonstrated an increase in kidney stones.

RECOMMENDATION 2: ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality evidence)

Although the direct evidence is insufficient to determine the appropriate duration of pharmacologic therapy, most studies that evaluated the benefit of treatment continued therapy for up to 5 years. Continuing treatment after the initial 5 years may be beneficial for some patients and may be appropriate after reassessing the risks and benefits of continuing therapy. Post hoc analysis from an RCT suggested 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 3: ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis. (Grade: weak recommendation; low-quality evidence)

Data that specifically apply to men are sparse. However, no evidence suggests that outcomes associated with pharmacologic treatment would differ between men and women if based on similar BMDs. Data for men are extrapolated from studies that included women with T scores of –2.5 or less or those who have experienced fragility fractures. Moderate-quality evidence from 1 study that detected fractures radiographically showed that zoledronic acid reduced vertebral fractures in osteoporotic men. In women, some bisphosphonates (alendronate, risedronate, and zoledronic acid) reduce vertebral, nonvertebral, and hip fractures. The overall quality of evidence was downgraded to low owing to indirectness. Bisphosphonates are associated with adverse effects, including mild gastrointestinal symptoms, atypical subtrochanteric fractures, and osteonecrosis of the jaw.

RECOMMENDATION 4: ACP recommends AGAINST bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women. (Grade: weak recommendation; low-quality evidence)

Current evidence does not show any benefit for bone density monitoring during treatment. Moderate-quality evidence showed that women treated with antiresorptive treatment (including bisphosphonates, raloxifene, and teriparatide) benefited from reduced fractures with treatment, even if there was no increase in BMD or if BMD decreased. There was no evidence for BMD monitoring for men.

RECOMMENDATION 5: ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women. (Grade: strong recommendation; moderate-quality evidence)

Moderate-quality evidence showed that menopausal estrogen treatment did not reduce fracture risk in postmenopausal women with established osteoporosis. Evidence from a previous systematic review showed that estrogen decreased fracture risk; however, many of these studies focused on postmenopausal women with low bone density, or on postmenopausal women in general rather than those with established osteoporosis. Estrogen treatment is associated with serious harms, such as increased risk for cerebrovascular accidents and venous thromboembolism, and these harms significantly outweigh the potential benefits. Although raloxifene has some benefit in reducing vertebral fractures, it does not reduce hip fracture or nonvertebral fractures and is associated with serious harms, including thromboembolism.

RECOMMENDATION 6: ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. (Grade: weak recommendation; low-quality evidence)

Low-quality evidence showed that treatment with risedronate in women with osteopenia (defined as a T score of –1.0 to –2.5) near the osteoporosis threshold (T score of –2.5) may reduce their fracture risk. This evidence comes from a post hoc analysis of 2-year follow-up data from 4 large RCTs of postmenopausal women with advanced osteopenia and no prevalent vertebral fractures that showed that treatment with risedronate significantly reduced the risk for fragility fracture compared with placebo (73% lower than placebo). This effect is similar to fracture reductions seen in women with osteoporosis undergoing the similar treatment. Duration of treatment in these studies was 1.5 to 3 years.

Although the current evidence is limited to a post hoc evaluation of risedronate in women with advanced osteopenia, the CGC believes that the benefit of fracture reduction is likely to be similar across all bisphosphonates, on the basis of data in osteoporotic women. However, the efficacy of other bisphosphonates has not been directly evaluated in osteopenic women, and no study has been conducted to primarily assess the effects of fracture prevention in women with osteopenia.

The rate of progressive bone loss and the risk for fracture range widely across the osteopenic spectrum and according to additional factors, such as age. The risk for severe adverse effects increases with prolonged use of bisphosphonates. Given the limited evidence supporting benefit, the balance of benefits and harms of treating osteopenic women is most favorable when the risk for fracture is high. Women younger than 65 years with osteopenia and women older than 65 years with mild osteopenia (T score between –1.0 and –1.5) will benefit less than women 65 years of age or older with severe osteopenia (T score < –2.0).

Clinicians can use their own judgment based on risk factors for fracture, or they can use a risk assessment tool. Several risk assessment tools, such as FRAX (World Health Organization Fracture Risk Assessment Tool), are available to predict fracture risk among untreated people with low bone density. Although FRAX is widely used, there is no evidence from RCTs demonstrating a benefit of fracture reduction when FRAX scores are used for treatment decision making. Factors that increase the risk for fracture in women include lower body weight, smoking, weight loss, family history of fractures, decreased physical activity, alcohol or caffeine use, low calcium and vitamin D intake, and corticosteroid use