Teriparatide: new preparation. Osteoporosis: less well evaluated than alendronic acid

(1) Oral alendronic acid is the reference drug for women with osteoporosis and a previous vertebral fracture. In a placebo-controlled trial in women who were also taking calcium and vitamin D, treatment with alendronic acid for three years reduced the incidence of symptomatic vertebral fractures (2.3% versus 5%) and wrist fractures (2.2% versus 4.1%) and, albeit with a lower level of evidence, the incidence of hip fractures (1.1% versus 2.2%). (2) Teriparatide, a biotech drug, reproduces the 34 N-terminal amino acids of parathormone. It is marketed in Europe for subcutaneous treatment of "proven" postmenopausal osteoporosis. (3) The cornerstone of the clinical evaluation dossier is a randomised placebo-controlled double-blind trial in 1637 women also taking calcium and vitamin D. The two doses of teriparatide (20 micrograms/day and 40 micrograms/day), given for a median of 19 months, reduced the risk of new radiologically documented vertebral fractures (about 4% versus 14% in the placebo group) and spinal pain (about 16% versus 23% in the placebo group), but not the risk of hip fracture. (4) In a double-blind trial in 146 postmenopausal women also taking calcium and vitamin D, 40 micrograms/day teriparatide given subcutaneously for 14 months increased spinal mineral bone density significantly more than 10 mg/day alendronic acid given orally. The trial was not designed to show a difference in clinical outcome (fractures). (5) The main adverse effects of teriparatide reported to date are nausea, headache, cramp, hypercalcemia and hyperuricemia. (6) A rat study showed an increased risk of osteosarcoma. This tumour is rare in humans, and the number of patients so far enrolled in clinical trials is insufficient to document a possible increase in risk associated with teriparatide. (7) The need for daily subcutaneous injections and for refrigeration of the prefilled syringes are two notable disadvantages of teriparatide therapy. (8) In practice, alendronic acid is better assessed and remains the reference treatment, combined with calcium and vitamin D, for secondary prevention of osteoporotic fracture in postmenopausal women.