What is true of bisphosphonates in the treatment of bone disorders?

From the Guidelines

Bisphosphonates are the recommended first-line treatment for primary osteoporosis to reduce the risk of fractures, due to their favorable balance of benefits, harms, patient values, and cost, as evidenced by high-certainty evidence from the American College of Physicians 1.

Key Points About Bisphosphonates

• They work by inhibiting osteoclast activity, which reduces bone resorption and increases bone mineral density.
• Common bisphosphonates include alendronate, risedronate, ibandronate, and zoledronic acid.
• These medications effectively reduce fracture risk in both postmenopausal women and men with osteoporosis.
• Bisphosphonates have long half-lives in bone tissue, allowing for flexible dosing regimens.
• Side effects may include gastrointestinal issues with oral formulations and rarely osteonecrosis of the jaw or atypical femur fractures with long-term use 1, 1.

Considerations for Use

• Bisphosphonates are contraindicated in patients with severe renal impairment (creatinine clearance <30-35 mL/min) 1.
• Hypocalcemia must be corrected before initiating therapy.
• Drug holidays are often considered after 3-5 years of treatment in moderate-risk patients and 5-10 years in high-risk patients.
• The risk of osteonecrosis of the jaw and atypical femoral fractures, although rare, should be considered, especially with long-term use 1.

Patient Education

• Patients should be advised to take oral bisphosphonates with plenty of water and to remain upright for at least 30 minutes after taking the medication to reduce the risk of esophageal irritation 1.
• Dental examination and prophylactic measures should be considered before starting bisphosphonate therapy due to the risk of osteonecrosis of the jaw 1.

From the FDA Drug Label

In patients with these conditions, serum calcium and symptoms of hypocalcemia should be monitored during therapy with alendronate sodium Presumably due to the effects of alendronate sodium on increasing bone mineral, small, asymptomatic decreases in serum calcium and phosphate may occur, especially in patients with Paget's disease, in whom the pretreatment rate of bone turnover may be greatly elevated, and in patients receiving glucocorticoids, in whom calcium absorption may be decreased Ensuring adequate calcium and vitamin D intake is especially important in patients with Paget's disease of bone and in patients receiving glucocorticoids. Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking bisphosphonates, including alendronate sodium. Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates that are approved for the prevention and treatment of osteoporosis

The following is true of bisphosphonates:

• Hypocalcemia must be corrected before initiating therapy
• Osteonecrosis of the jaw has been reported in patients taking bisphosphonates
• Atypical femoral fractures have been reported in bisphosphonate-treated patients
• Musculoskeletal pain has been reported in patients taking bisphosphonates
• Bisphosphonates can cause upper gastrointestinal adverse reactions, such as esophagitis and gastritis
• Ensuring adequate calcium and vitamin D intake is important in patients taking bisphosphonates, especially those with Paget's disease or receiving glucocorticoids 2 2 3

From the Research

Characteristics of Bisphosphonates

• Bisphosphonates are a class of drugs used to treat bone disorders, including osteoporosis 4, 5, 6.
• They work by suppressing bone resorption and increasing bone strength, which reduces the risk of fractures 5, 6.
• There are several types of bisphosphonates, including alendronate, risedronate, ibandronate, and zoledronic acid, which are approved in the United States 4.
• Bisphosphonates can be administered orally or intravenously, with varying dosing intervals 4, 6.

Efficacy of Bisphosphonates

• Bisphosphonates have been shown to reduce the risk of vertebral fractures in women with postmenopausal osteoporosis 4, 7, 8.
• Alendronate, risedronate, and zoledronic acid have also been shown to reduce the risk of nonvertebral and hip fractures 4, 7, 8.
• Zoledronic acid has been found to be the most effective bisphosphonate in preventing vertebral fractures, nonvertebral fractures, and any fractures 7, 8.
• The efficacy of bisphosphonates is maintained during long-term treatment, with clinical trial extensions of up to 10 years showing sustained efficacy 4.

Comparative Efficacy of Bisphosphonates

• Network meta-analyses have compared the efficacy of different bisphosphonates in preventing fractures, with zoledronic acid ranking first in preventing vertebral fracture, hip fracture, and any fracture 7, 8.
• Alendronate and zoledronic acid have been found to be the most effective in preventing hip fractures 8.
• The comparative efficacy of bisphosphonates may depend on the specific population being treated and the dosing regimen used 5, 6.