Primary and secondary options for therapy of osteoporosis.
Identify indications for initiating osteoporosis treatment.
List interventions in reducing fracture risk.
List first line and second line osteoporosis therapy.
Treating primary osteoporosis
Treatment may be indicated even if a person does not meet clinical or radiological criteria for osteoporosis as the goal of treatment is to reduce the risk of fractures. Initiation of medical therapy is based on future fracture risk and not purely a radiographic finding (see Geriatric Fast Facts: Osteoporosis Screening and Diagnosis).
Treatment should include adequate calcium and vitamin D supplementation, mitigation of risk factors causing bone loss and reduction of fall risk (Table 1) as well as potentially other pharmacotherapy.
Indications for pharmacotherapy with a bisphosphonate, a RANKL (receptor activator of nuclear factor kappa-B ligand) inhibitor or an anabolic agent include:
Diagnosis of osteoporosis (as defined in Geriatric Fast Facts: Osteoporosis Screening and Diagnosis)
Osteopenia (T-score -1.0 to -2.4) and 10-year probability of hip fracture >3 percent or major osteoporosis-related fracture >20 percent based on the WHO FRAX calculator (https://www.shef.ac.uk/FRAX/tool.jsp).
Bisphosphonates are effective first line treatments for osteoporosis. They come in oral (alendronate, risedronate, and ibandronate) or intravenous formulations (zoledronic acid and ibandronate). Prior to initiating therapy with a bisphosphonate, it is imperative to check kidney function (requires GFR>35 mL/min/1.73 m2) and vitamin D status (level should be >25ng/mL to reduce the risk of hypocalcemia). A history of severe gastroparesis, esophagitis, stricture or other esophageal or stomach disorder may be relative contraindications to oral therapy. Side effects may include myalgias, fever, and fatigue, especially for IV preparations. Rare, but severe, side effects may include atypical fractures and osteonecrosis. Atypical fractures are rare and are associated with extended treatment (>10yrs) which is why a drug “holiday” (discontinuation) is introduced after 5 years of therapy. Osteonecrosis of the jaw is rare, with most cases occurring in cancer patients or in patients who were treated with high doses of IV bisphosphonates.6
Denosumab (a RANKL inhibitor) is not considered as initial therapy for most patients with osteoporosis though it may be appropriate for patients at high risk for fracture who have a contraindication to, or unresponsiveness towards, bisphosphonates, or those patients whose GFR < 35mL/min/1.73m2. This medication is administered every 6 months by subcutaneous injection. The side effects are similar to bisphosphonates and include the risk of atypical fractures and osteosarcoma. Risk of infections, including skin, abdominal, lung, and urinary system are slightly more common (4%) and if developed while on therapy are a reason for discontinuation of any future treatments.
Teriparatide is an anabolic agent stimulating bone formation through activation of bone remodeling. This medication is not considered initial therapy for most patients and is reserved for those who have severe osteoporosis (T-score of -3.5 or below even in the absence of fractures, or T-score of -2.5 or below plus a fragility fracture), have a contraindication to bisphosphonates, or failed other osteoporosis therapies. Treatment requires daily subcutaneous injections. Side effects may include bone pain, injection site irritation, and hypercalcemia. Rare risks include osteosarcoma. Treatment duration is two years.
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