The short term effect of a single Parathyroid Hormone (PTH) injection on the healing of stress fractures

Abstract

Stress, or fatigue, fractures (Sfx), occur as a result of repetitive non-traumatic cyclic loading [1]. 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)[1, 2]. 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. Sixteen female wistar rats 300 g were allocated to PTH and vehicle (VEH) groups. 24 hours after Sfx, PTH 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. Ulnae were harvested two weeks after loading, dissected, processed for histology and stained with Toluidine blue and for TRAP. Histomorphometry was conducted using OsteomeasureTM. There were no differences between groups for cortical area, woven bone area or length of fracture. There was a trend for increased SFx porosity (resorption), erosion and area of new bone formation in PTH groups; but significantly increased osteoclast number when compared to VEH group (P<0.01). 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.