Category:Osteoporosis medications: Difference between revisions

An osteoporosis medication is a medicine used to prevent fragility fracture in patients with low bone density or with a prior fragility fracture. The category is organised around two complementary pharmacological strategies: antiresorptive therapy that slows bone loss (the bisphosphonates, the RANKL antibody denosumab, the selective estrogen-receptor modulators, the older calcitonin, hormone replacement), and anabolic therapy that stimulates bone formation (the parathyroid hormone analogues teriparatide and abaloparatide, and the sclerostin antibody romosozumab whose dual mechanism combines both). The medicines are supported by foundational mineral supplementation (calcium and vitamin D, the substrate of bone matrix and the regulator of calcium absorption).

The clinical history of osteoporosis pharmacology is told under antiresorptives and bisphosphonates for the bone-loss-prevention side, and under hormones for the parathyroid-hormone analogues that drive bone formation. The contemporary clinical-pharmacology framing of osteoporosis is described here: the disease, the risk-stratification, the treatment thresholds, and the algorithm by which the available medicines are deployed.

The disease was formally described by the American endocrinologist Fuller Albright of the Massachusetts General Hospital in 1941, who established the connection between postmenopausal estrogen loss and the resulting bone loss as the dominant cause of vertebral and hip fractures in elderly women.^[1] Albright's recommendation of estrogen replacement was the standard treatment for forty years. The 1994 World Health Organization operational definition of osteoporosis (a femoral-neck T-score of 2.5 standard deviations or more below the mean of young adult women, measured by dual-energy X-ray absorptiometry) gave the contemporary diagnostic framework; the 2008 introduction of the FRAX (Fracture Risk Assessment) tool by John Kanis and the WHO Collaborating Centre at Sheffield gave a country-specific 10-year fracture-probability calculator that integrates T-score with clinical risk factors (age, sex, prior fracture, parental hip fracture, smoking, alcohol, glucocorticoid use, rheumatoid arthritis, secondary causes of osteoporosis) and now drives treatment-threshold decisions in many guidelines.

The contemporary indications for pharmacological treatment of osteoporosis are well-defined. Treatment is recommended in postmenopausal women and men age 50 and older when: (1) a prior fragility hip or vertebral fracture has occurred, regardless of T-score; (2) the femoral-neck or total-hip T-score is -2.5 or below; or (3) the T-score is in the osteopenic range (-1.0 to -2.5) and the FRAX 10-year probability of major osteoporotic fracture exceeds country-specific thresholds (in the United States, 20 percent for major osteoporotic fracture or 3 percent for hip fracture). Patients on chronic systemic glucocorticoids (7.5 mg/day prednisone equivalent for over 3 months) are treated more aggressively because of the disproportionate fracture risk that medicine produces.

The contemporary treatment algorithm has been progressively refined. For postmenopausal women and men age 50 and older at significant but not very high risk, first-line therapy is oral bisphosphonate (alendronate or risedronate), with intravenous zoledronate or subcutaneous denosumab for patients intolerant of oral bisphosphonate or with renal impairment. For patients at very high risk (multiple vertebral fractures, hip fracture, T-score below -3.0, FRAX above 30 percent for major osteoporotic fracture), anabolic-first therapy with teriparatide (Forteo, twice-daily subcutaneous injection for up to 2 years), abaloparatide (Tymlos, daily subcutaneous injection), or romosozumab (Evenity, monthly subcutaneous injection for 12 months) followed by antiresorptive maintenance produces greater bone-density gain and greater fracture-risk reduction than antiresorptive monotherapy. Sequential therapy with the anabolic agent first and the antiresorptive second is now standard for this high-risk population.

The duration-of-treatment question is one of the central clinical decisions in osteoporosis care. For oral bisphosphonates, a five-year course followed by a "medicine holiday" of 2-5 years (during which antifracture benefit persists because of the long bone half-life of the bisphosphonate) is the standard for most patients; high-risk patients may continue beyond 5 years. For annual intravenous zoledronate, 3 years followed by a holiday is standard, with 6 years for higher-risk patients. For denosumab, no medicine holiday is recommended: abrupt discontinuation produces a rebound of bone resorption with multiple vertebral fractures within months, and patients who discontinue denosumab for any reason must be transitioned to a bisphosphonate to lock in the gains. For teriparatide and abaloparatide, the 24-month lifetime treatment limit (osteosarcoma concern from rat lifetime exposure, not directly seen in humans but the regulatory caution remains) defines the duration; sequential transition to an antiresorptive is required to maintain the gains. For romosozumab, 12 months of treatment is the maximum (the ARCH trial endpoint), again followed by antiresorptive maintenance.

The supportive-care medicines complete the regimen. Calcium supplementation (1000-1200 mg per day, including dietary sources) and vitamin D supplementation (800-2000 IU per day, with a 25-hydroxyvitamin D target above 30 ng/mL) are foundational and are co-prescribed with every active osteoporosis regimen; the supplementation may be insufficient as monotherapy for established osteoporosis but is necessary to optimise the effect of antiresorptive and anabolic medicines. Physical activity (weight-bearing exercise, resistance training, balance training to reduce fall risk), fall-risk modification (review of sedating medicines, home-safety assessment), and avoidance of bone-toxic medicines (chronic glucocorticoids, aromatase inhibitors in selected patients, GnRH agonist therapy in prostate cancer) are part of standard non-pharmacological management.

By mechanism:

• Antiresorptive (cross-indexed under antiresorptives):
  • Bisphosphonates: oral alendronate, risedronate, ibandronate; intravenous ibandronate (quarterly) and zoledronate (annual)
  • RANKL antibody: denosumab (Prolia, 60 mg subcutaneous every 6 months)
  • SERMs: raloxifene (vertebral-fracture reduction; breast-cancer chemoprevention bonus indication), bazedoxifene
  • Calcitonin: salmon calcitonin nasal spray (limited current use)
  • Hormone replacement: estrogen-progestin combinations (cross-indexed under hormone replacement therapy)
• Anabolic (cross-indexed under hormones for the PTH analogues):
  • PTH analogues: teriparatide (Forteo, daily SC for up to 2 years), abaloparatide (Tymlos, daily SC)
  • Sclerostin antibody (dual anabolic + antiresorptive): romosozumab (Evenity, monthly SC for 12 months)
• Foundational mineral supplementation:
  • Calcium supplements: calcium carbonate (food-dependent absorption; OTC); calcium citrate (food-independent; smaller doses required for the elderly and PPI users)
  • Vitamin D: cholecalciferol (D3), ergocalciferol (D2), the active calcitriol in selected indications (renal disease)
  • Magnesium where deficient

The boundary of this category is "medicine prescribed primarily to prevent or treat osteoporotic fracture." Medicines used in Paget's disease of bone (the bisphosphonates at different dose schedules), osteogenesis imperfecta (intravenous pamidronate or zoledronate in childhood), renal osteodystrophy (vitamin D analogues, calcimimetic cinacalcet, phosphate binders), and hypoparathyroidism (PTH replacement) are cross-listed where the medicines overlap, but their primary classification is by indication. The bone-targeting radiopharmaceuticals (radium-223 for prostate cancer bone metastases, samarium-153 EDTMP for bone-pain palliation) are not osteoporosis medicines and are listed under antineoplastics. The medicines that secondarily cause osteoporosis (chronic glucocorticoids, aromatase inhibitors, GnRH agonists, the older anticonvulsants, proton pump inhibitors, SSRIs) are noted as risk factors but are not osteoporosis medicines.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.