Antiresorptive, Anabolic, And Dual-Action Osteoporosis Drugs

Osteoporosis drugs can be divided into three categories: antiresorptive drugs that slow bone breakdown (resorption), anabolic drugs that build new bone, and dual-action drugs that both slow bone resorption and build new bone. Most approved osteoporosis drugs are antiresorptive. These slow bone loss and help fill in the remodeling spaces. All antiresorptive agents reduce the risk of vertebral (spinal) fractures and reduce markers of bone turnover. These markers are substances in the blood and urine that reflect the activity of the bone cells involved in breakdown and formation.

Antiresorptive medications include bisphosphonates, selective estrogen receptor modulators (SERMs), hormone replacement therapy (HRT), and calcitonin. Bisphosphonates include alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast). The only approved SERM is raloxifene (Evista). HRT includes several agents: Premarin, Prempro, Estrace, Estraderm, and Climara. Calcitonin is a polypeptide hormone secreted by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish. Miacalcin® (calcitonin-salmon) Nasal Spray is a synthetic polypeptide of 32 amino acids in the same linear sequence that is found in calcitonin of salmon origin. Miacalcin is also available as an injection.

The newest drug in the antiresorptive category is denosumab (Prolia), an injection administered subcutaneously once every six months. Prolia binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Prolia prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.

In clinical trials in women with postmenopausal osteoporosis, treatment with Prolia resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry. The significance of these findings and the effect of long-term treatment with Prolia are unknown. The long-term consequences of the degree of suppression of bone remodeling observed with Prolia may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing.

Antiresorptives do not build bone beyond what is produced to help fill the remodeling spaces. Bone-building (anabolic) drugs, on the other hand, stimulate bone formation by increasing the activity of the cells known as osteoblasts. The only such medication approved in the U.S.A. for treating osteoporosis is teriparatide (Forteo), a form of human parathyroid hormone (PTH). The drug comes as a daily injection, which can be self-administered. PTH produces larger increases in BMD than antiresorptives do. It also improves bone microarchitecture. However, it is prescribed for no more than about two years because its long-term safety and efficacy are unknown. Most experts recommend that antiresorptive drugs be stopped during PTH therapy and restarted after the course of PTH is complete.

Strontium ranelate is a compound that incorporates the element strontium, which is found in trace amounts throughout the skeleton. Results from Phase III trials conducted by French researchers suggest that strontium ranelate may reduce vertebral fractures about as well as bisphosphonates. The drug is believed to work by decreasing bone breakdown and increasing bone buildup. This prescription drug is not available in the U.S.A., but strontium citrate can be purchased as a supplement.

My opinion is that the antiresorptive drugs are flawed models as osteoporosis drugs. If we keep slowing bone breakdown without building new bone, we eventually end up with very old, weak bones. Long-term suppression of bone remodeling by Fosamax and other bisphosphonates has led to osteonecrosis of the jaw and atypical femur fractures in some patients. Better models are bone-building (anabolic) drugs (i.e. Forteo) and dual-action agents (i.e. strontium ranelate, strontium citrate) that decrease bone breakdown and increase bone buildup.

http://www.health.harvard.edu/newsweek/Update_on_osteoporosis_drugs.htm
http://www.rxlist.com/miacalcin-drug.htm
http://www.rxlist.com/prolia-drug.htm