Fracture Healing with Current and Emerging Osteoporosis Therapies

The failure rate for fracture fixation in patients with osteoporosis has been estimated to be 10–25%. An agent that improves bone repair, fracture healing, and fixation of surgical hardware would be beneficial in the management of fractures. A consensus statement released by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) addressed fracture healing with current and emerging osteoporosis therapy.

The ESCEO concluded that bisphosphonates (Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa) and raloxifene (Evista) did not impair fracture healing.

Preclinical studies and several case reports suggested that strontium ranelate might enhance fracture healing.

Studies with teriparatide (Forteo) had mixed results, but overall were consistent with a beneficial effect on fracture healing.

Clinical trials with denosumab (Prolia) have shown no adverse effects on fracture healing.

Sclerostin monoclonal antibody therapy has been shown to enhance fracture healing in rats and cynomolgus monkeys. Although several phase II studies to investigate the effects of romosozumab (an antisclerostin therapy) on fracture healing in humans have been conducted [ClinicalTrials.gov identifiers: NCT00907296, NCT01081678], there is currently no ongoing effort to pursue regulatory approval of this agent for acceleration of fracture healing.

You will note that, among the current therapies, only strontium ranelate, which is not available in the USA or Canada, and teriparatide may enhance fracture healing. I believe strontium citrate has the same beneficial effect on fracture healing because it is the strontium that increases bone mineral density and improves bone microarchitecture. 

Role of Sclerostin in Bone and Cartilage and Its Potential as a Therapeutic Target in Bone Diseases, E. Michael Lewiecki, MD, FACP, FACE, Ther Adv Musculoskel Dis. 2014;6(2):48-57.

Goldhahn, J., Feron, J., Kanis, J., Papapoulos, S., Reginster, J., Rizzoli, R. et al. (2012) Implications for fracture healing of current and new osteoporosis treatments: an ESCEO consensus paper. Calcif TissueInt 90: 343–353.

The Osteoporosis Patient With Renal Insufficiency

A German paper by G. Lehmann, G. Hein, and G. Wolf addresses the osteoporosis patient with renal insufficiency and what has to be taken into account in the selection and administration of medications for osteoporosis. Because the incidence of osteoporosis and renal insufficiency increases with age, the use of antiosteoporotic drugs approved for long-term administration in patients with inadequate renal function is a cause for concern. In the dose approved for the treatment of osteoporosis, oral bisphosphonates and i.v. ibandronate (3 mg every 12 weeks) are considered safe in patients with glomerular filtration rate (GFR) > 30 ml/min. Treatment with strontium ranelate and the osteoanabolic substance teriparatide is not altered by impaired renal function until GFR falls below 30 ml/min. Efficiency of the selective estrogen receptor modulator (SERM) raloxifene is not altered by renal function.
http://www.ncbi.nlm.nih.gov/pubmed/16924452