Monitoring Different Stages of Bone Remodeling and Healing of Stress Fractures (SFx) in Rat Ulnae Throughout a Period of Ten Weeks Following a Single Parathyroid Hormone (PTH) Injection

Abstract

Introduction/Aim: Stress, or fatigue, fractures (Sfx), occur as a result of repetitive non-traumatic cyclic loading [1]. They are common in athletes, soldiers and dancers. 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. Methods: Seventy two female wistar rats 300 g were allocated to PTH and vehicle (VEH) groups. 24 hours after Sfx loading, PTH group received a single dose of hPTH-(1-34) peptide (Sigma-Aldrich). Rats in PTH and VEH groups were further divided into four groups based on the time their ulnae were harvested. Ulnae were harvested at one week, two weeks, six weeks and ten weeks after loading. All ulnae were dissected, processed for histology and stained with Toluidine blue and TRAP for osteoclasts count. Histomorphometry was conducted using OsteomeasureTM. Results: 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 after one and two weeks; but significantly increased osteoclast number when compared to the VEH group (P<0.01). Six weeks post SFx loading woven bone area, healed boned bone area, Basic Multicellular Unit (BMU) size, healed bone area, healed bone perimeter and percentage healing were increased in PTH group. Woven bone apposition rate was significantly higher two weeks post SFx loading in PTH group (P<0.01). Ten weeks post SFx, bone healing parameters further increased in PTH group. Conclusion: These data provide evidence that a single PTH injection, 24 hours after SFx initiation, results in active changes in dynamics of bone remodeling that accelerates healing.