Fri., 10/19/07 Basic Science, Paper #40, 4:17 pm OTA-2007
Parathyroid Hormone and Alendronate Improve Osteotomy Healing in an Osteoporotic Rat Model
Jose B. Toro, MD (n); Andy Tomin, BS (n); Kathleen Meyers MS (n); Brett Shore, MD (n);
Margareth Lauerman, MD (n); Paul Issack, MD, PhD (n); Joseph Lane, MD (n);
Hospital for Special Surgery, New York, New York, USA
Purpose: Bisphosponates and parathyroid hormone (PTH) are common medications to treat osteoporosis. There are minimal clinical data on the effect of these pharmaceuticals for treatment of diaphyseal fracture healing in the osteoporotic population.
It was hypothesized that pretreatment with bisphosphonates (1) would compromise fracture healing, (2) that postfracture treatment with PTH would produce superior results in fracture healing when compared to alendronate-treated animals or controls, and (3) that PTH would reverse pretreatment inhibition of bone metabolism secondary to bisphosphonates therapy.
Methods: 126 ovarectomized Sprague-Dawley rats were used and divided into two groups: group 1 (n = 63) received 10 μg/kg/week of alendronate by subcutaneous injection, and group 2 (n = 63) served as controls (no pretreatment). Osteotomies were performed on all rats at 6 weeks postovariectomy. At the time of surgery, the group that received pretreatment with alendronate (group 1) was randomly divided into three groups: group 1a (n = 21) continued weekly injections with alendronate, group 1b (n = 21) received daily injections with rhPTH (Forteo) (10 μg/kg/day), and group 1c (n = 21) received no treatment. The rats that did not receive alendronate pretreatment were randomly divided into the same three postsurgical treatment groups (groups 2a-c). All animals were euthanized 6 weeks after surgery.
Results: The union rates for animals pretreated with alendronate were as follows: group 1a 82%, and group 1b 78% (P = 0.021), compared to group 1c 44%. For the rats that did not receive pretreatment (group 2), the union rates were groups 2a and 2b 56%, and group 2c 41%. Estrogen-deficient rats from the control group showed a 59% nonunion rate at 6 weeks. Those rats that received pharmacologic intervention before osteotomy presented with a nonunion rate of 54%, statistically insignificant compared to the control group.
Postosteotomy intervention with either alendronate or PTH was statistically significant for all samples that received alendronate before surgery. Also, estrogen-deficient rodents that received alendronate or PTH did decrease the rate of nonunion compared to estrogen-deficient rats that received alendronate before osteotomy and was stopped after intervention or the control group.
Conclusions and Significance: Pretreatment with alendronate and posttreatment either with alendronate or PTH prevented the development of nonunion. Pretreatment with alendronate did not inhibit osteotomy healing. In the osteoporotic animal model, both PTH and alendronate are enhancers of osteotomy healing.
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• The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an “off label” use). ◆FDA information not available at time of printing.