The main efficacy criterion for drugs against osteoporosis is protection against fractures. Many resorption-inhibiting agents meet this criterion, including estrogens, alendronate, risedronate, raloxifene, calcitonin, and calcium-vitamin D supplements). Conversely, among anabolic agents, only parathyroid hormone (PTH) is known to reduce the fracture risk, the mechanism being increased bone matrix production by osteoblasts with no alterations in the mechanical properties of bone. Although fluoride salts induce a marked increase in bone mineral density (BMD), there is no evidence that this protects against vertebral or peripheral fractures. Growth hormone, IGF-I, statins, and strontium ranelate are under investigation. A recent controlled clinical trial in 1637 women with osteoporosis showed that daily subcutaneous injections of PTH (1-34) (20 or 40 μg) for 21 months reduced the fracture risk. With 20 μg/day, the reductions were 65% for vertebral fractures and 57% for extravertebral fractures, 11% of patients had moderate postinjection hypercalcemia, and BMD increased by 9% at both the lumbar spine and the femoral neck. These findings open up the exciting possibility that PTH used alone or in combination with resorption-inhibiting agents may be helpful. To date, PTH is the only anabolic agent that has proved capable of reducing the risk of vertebral and extravertebral fractures in women with established postmenopausal osteoporosis.