Unstable slipped capital femoral epiphysis (SCFE) has an increased incidence of avascular necrosis (AVN). The purpose of this study was to determine if early identification and intervention for AVN may help preserve the femoral head.

We retrospectively reviewed 48 patients (50 hips) with unstable SCFE managed between 2000 and 2014. Based on two different protocols during the same time period, 17 patients (17 hips) had a scheduled MRI between 1 and 6 months from initial surgery, with closed bone graft epiphysiodesis (CBGE) or free vascularised fibular graft (FVFG) if AVN was diagnosed. Thirty-one patients (33 hips) were evaluated by plain radiographs. Outcomes analysed were Steinberg classification and subsequent surgical intervention. We defined Steinberg class IVC as failure in treatment because all of the patients referred for osteotomy, arthoplasty, or arthrodesis in our study were grade IVC or higher.

Overall, 13 hips (26%) with unstable SCFE developed AVN. MRI revealed AVN in 7 of 17 hips (41%) at a mean of 2.5 months postoperatively (range, 1.0 to 5.2 months). Six hips diagnosed by MRI received surgical intervention (4 CBGE, 1 FVFG, and 1 repinning due to screw cutout) at a mean of 4.1 months (range, 1.3 to 7.2 months) postoperatively. None of the 4 patients treated with CBGE within two months postoperatively progressed to stage IVC AVN. The two patients treated after four months postoperatively both progressed to stage VC AVN. Radiographically diagnosed AVN occurred in 6 of 33 hips (18%) at a mean of 6.8 months postoperatively (range, 2.1 to 21.1 months). One patient diagnosed with stage IVB AVN at 2.4 months had screw cutout and received CBGE at 2.5 months from initial pinning. The remaining 5 were not offered surgical intervention. Five of the 6 radiographically diagnosed AVN, including the one treated with CBGE, progressed to stage IVC AVN or greater.

None of the 4 patients with unstable SCFE treated with CBGE within 2 months post pinning developed grade IVC AVN, while all patients treated with other procedures after 2 months developed IVC or greater AVN. Early detection and treatment of AVN after SCFE may alter the clinical and radiographic progression.

Bone morphogenetic proteins (BMPs) are able to induce osteogenic differentiation in many cells, including muscle cells. However, the actual contribution of muscle cells to bone formation and repair is unclear. Our objective was to examine the capacity of myogenic cells to contribute to BMP-induced ectopic bone formation and fracture repair.

Osteogenic gene expression was measured by quantitative PCR in osteoprogenitors, myoblasts, and fibroblasts following BMP-2 treatment. The MyoD-Cre x ROSA26R and MyoD-Cre x Z/AP mouse strains were used to track the fate of MyoD+ cells in vivo. In these double-transgenic mice, MyoD+ progenitors undergo a permanent recombination event to induce reporter gene expression. Ectopic bone was produced by the intramuscular implantation of BMP-7. Closed tibial fractures and open tibial fractures with periosteal stripping were also performed. Cellular contribution was tracked at one, two and three week time points by histological staining.

Osteoprogenitors and myoblasts exhibited comparable expression of early and late bone markers; in contrast bone marker expression was considerably less in fibroblasts. The sensitivity of cells to BMP-2 correlated with the expression of BMP receptor-1a (Bmpr1a). Pilot experiments using the MyoD-Cre x Rosa26R mice identified a contribution by MyoD expressing cells in BMP-induced ectopic bone formation. However, false positive LacZ staining in osteoclasts led us to seek alternative systems such as the MyoD-cre x Z/AP mice that have negligible background staining. Initially, a minor contribution from MyoD expressing cells was noted in the ectopic bones in the MyoD-cre x Z/AP mice, but without false positive osteoclast staining. Soft tissue trauma usually precedes the formation of ectopic bone. Hence, to mimic the clinical condition more precisely, physical injury to the muscle was performed. Traumatising the muscle two days prior to BMP-7 implantation: (1) induced MyoD expression in quiescent satellite cells; (2) increased ectopic bone formation; and (3) greatly enhanced the number of MyoD positive cells in the ectopic bone. In open tibial fractures the majority of the initial callus was MyoD+ indicating a significant contribution by myogenic cells. In contrast, closed fractures with the periosteum intact had a negligible myogenic contribution.

Myoblasts but not fibroblasts were highly responsive to BMP stimulation and this was associated with BMP receptor expression. Our transgenic mouse models demonstrate for the first time that muscle progenitors can significantly contribute to ectopic bone formation and fracture repair. This may have translational applications for clinical orthopaedic therapies.