A comparison between the effects of a single Parathyroid Hormone (PTH) injection on the healing of stress fractures after 2 and 6 weeks.

Objectives: Stress, or fatigue, fractures (Sfx), occur as a result of repetitive non-traumatic cyclic loading. They are common in professional athletes, soldiers and dancers, and repair via a process of direct remodelling. Anti-inflammatory drugs (NSAIDs), commonly used in SFx patients, retard SFx healing, as do bisphosphonates (BPs). Parathyroid hormone (PTH) has an anabolic effect that can accelerate bone remodelling and counteract effects of BP. Therefore, our aim was to investigate the short-term effect of a single PTH injection on the healing of SFx.
Methods: Thirty four female wistar rats 300 g were allocated to PTH and vehicle (VEH) groups. 24 hours after Sfx, PTH group received a single dose of hPTH-(1-34) peptide (Sigma-Aldrich) (8 μg/100g) dissolved in 0.9% saline with 1% rat heat-inactivated serum. SFx was created in the right ulna of both groups using cyclic end-loading. We used the ulnar SFx model, allowing scrutiny of focal remodeling with a known time course and precise anatomical location. Both groups had an ulnar stress fracture induced in a single session (Figure 1). Ulnae of half of the groups were harvested two weeks after loading, the other half were harvested six weeks after loading. All ulnae were dissected, processed for histology and stained with Toluidine blue and TRAP for osteoclasts count. Histomorphometry was conducted using Osteomeasure^TM.
Results: There were no differences between groups for cortical area, or length of fracture. After 2 weeks: There was a trend for increased SFx porosity (resorption), erosion and woven bone formation in PTH group; but significantly increased osteoclast number when compared to the VEH group (P<0.01). After 6 weeks: There was a statistically significant difference with more woven bone and porosity areas in PTH group. Comparing the results of the 2 weeks and 6 weeks cohorts showed a significant increase in the number of osteoclasts in the 2 weeks cohort and a significant increase in healed bone area in the 6 weeks cohort.
Conclusions: These data provide evidence that a single PTH injection, 24 hours after SFx initiation, results in active changes in dynamics of bone remodelling that may accelerate healing. Additional data is now required to demonstrate the long-term effect on healing time, and potential for daily PTH injections on the healing of SFx.