BMP-1 is the major procollagen-C-peptidase activating, besides fibrillar collagen types I-III, several enzymes and growth factors involved in the generation of extracellular matrix. This study investigated the effect of adding and inhibiting BMP-1 directly post fracture.

Standardised femoral fractures were stabilized by an intramedullary nail in 12 week-old female C57Bl/6J mice. We injected either 20 µL recombinant active BMP-1, activity buffer or the BMP-1 specific inhibitor “sizzled”. After 7, 14 and 28 days, mice were sacrificed. Femurs were dissected and paraffin slides were prepared. Callus composition was divided into soft tissue, mineralized and cartilaginous callus. Murine MC3T3 pre-osteoblastic cells were kept in culture adding BMP-1 and sizzled during osteoblastic differentiation. Putative cytotoxicity was determined using MTT-vitality assay. Cell calcification, collagen deposition, and BMP-2 and myostatin protein quantity were characterized.

Adding BMP-1 displayed a weak positive effect on the outcome. After 7 days, more mineralised callus was present, meanwhile the cartilaginous callus was apparently remodelled at higher rate. In the case of BMP-1 inhibition, we observed more cartilaginous callus, which may indicate reduced stability. In cell culture, we could observe a high interference with mineralisation capabilities depending on the stage of osteoblastic development when adding BMP-1 or inhibiting it. Addition and inhibition impaired myostatin (anti-osteogen) and BMP-2 (pro-osteogen) expression.

Interfering with BMP-1 homeostasis in this early stage of fracture repair seems to have rather negative effects. Inhibition apparently yields lower callus quality while the addition of BMP-1 does not significantly accelerate the healing outcome. Cell culture experiments show that BMP-1 application after 7 days of healing leads to higher collagen output but has no effect on mineralisation. This may suggest that BMP-1 application at a later time-point may lead to more pronounced beneficial effects on fracture repair.

Metal-on-metal hip resurfacing prostheses are a relatively recent intervention for relieving the symptoms of common musculoskeletal diseases such as osteoarthritis. While some short term clinical studies have offered positive results, in a minority of cases there is a recognised issue of femoral fracture, which commonly occurs in the first few months following the operation. This problem has been explained by a surgeon's learning curve and notching of the femur but, to date, studies of explanted early fracture components have been limited. Tribological analysis was carried out on fourteen retrieved femoral components of which twelve were revised after femoral fracture and two for avascular necrosis (AVN). Eight samples were Durom (Zimmer, Indiana, USA) devices and six were Articular Surface Replacements (ASR, DePuy, Leeds, United Kingdom). One AVN retrieval was a Durom, the other an ASR. The mean time to fracture was 3.4 months. The AVNs were retrieved after 16 months (Durom) and 38 months (ASR). Volumetric wear rates were determined using a Mitutoyo Legex 322 co-ordinate measuring machine (scanning accuracy within 1 micron) and a bespoke computer program. The method was validated against gravimetric calculations for volumetric wear using a sample femoral head that was artificially worn in vitro. At 5mm3, 10mm3, and 15mm3 of material removal, the method was accurate to within 0.5mm3. Surface roughness data was collected using a Zygo NewView500 interferometer (resolution 1nm). Mean wear rates of 17.74mm3/year were measured from the fracture components. Wear rates for the AVN retrievals were 0.43mm3/year and 3.45mm3/year. Mean roughness values of the fracture retrievals (PV = 0.754nm, RMS = 0.027nm) were similar to the AVNs (PV = 0.621nm, RMS = 0.030nm), though the AVNs had been in vivo for significantly longer. Theoretical lubrication calculations were carried out which found that in both AVN retrievals and in seven of the twelve cases of femoral fracture the roughening was sufficient to change the lubrication regime from fluid film to mixed. Three of these surfaces were bordering on the boundary lubrication regime. The results show that even before the femoral fracture, wear rates and roughness values were high and the implants were performing poorly

Wear debris induced osteolysis is a recognized complication in conventional metal-on-polyethylene hip arthroplasty. One method of achieving wear reduction is through the use of metal-on-metal articulations. One of the latest manifestations of this biomaterial combination is in designs of hip resurfacing which are aimed at younger, more active patients. But, do these metal-on-metal hip resurfacings show low wear when implanted into patients?. Using a Mitutoyo Legex 322 co-ordinate measuring machine (scanning accuracy less than 1 micron) and a bespoke computer program, volumetric wear measurements for retrieved Articular Surface Replacements (ASR, DePuy) metal-on-metal hip resurfacings were undertaken. Measurements were validated against gravimetric calculations for volumetric wear using a sample femoral head that was artificially worn in vitro. At 5mm3, 10mm3, and 15mm3 of material removal, the method was shown to be accurate to within 0.5mm3. Thirty-two femoral heads and twenty-two acetabular cups were measured. Acetabular cups exhibited mean volumetric wear of 29.00mm3 (range 1.35 - 109.72mm3) and a wear rate of 11.02mm3/year (range 0.30 - 63.59mm3/year). Femoral heads exhibited mean wear of 22.41mm3 (range 0.72 - 134.22mm3) and a wear rate of 8.72mm3/year (range 0.21 - 31.91mm3/year). In the 22 cases where both head and cup from the same prosthesis were available, mean total wear rates of 21.66mm3/year (range 0.51 - 95.50mm3/year) were observed. Revision was necessitated by one of five effects; early femoral neck fracture (4 heads), avascular necrosis (AVN) (2 heads, 1 cup), infection (1 head, 1 cup), adverse reaction to metal debris (ARMD) (19 heads, 18 cups) or ARMD fracture (6 heads, 2 cups). Mean paired wear rates for the AVN and infection retrievals were 0.51mm3/year and 3.98mm3/year respectively. In vitro tests typically offer wear rates for metal-on-metal devices in the region of 2-4mm3. Mean paired wear rates for ARMD and ARMD fracture were 17.64mm3/year and 68.5mm3/year respectively, significantly greater than those expected from in vitro tests. In the 4 cases of early fracture, only the heads were revised so a combined wear rate calculation was not possible. The heads exhibited mean wear rate of 8.26mm3/year. These high wear rates are of concern

The cortical strains on the femoral neck and proximal femur were measured before and after implantation of a resurfacing femoral component in 13 femurs from human cadavers. These were loaded into a hip simulator for single-leg stance and stair-climbing. After resurfacing, the mean tensile strain increased by 15% (95% confidence interval (CI) 6 to 24, p = 0.003) on the lateral femoral neck and the mean compressive strain increased by 11% (95% CI 5 to 17, p = 0.002) on the medial femoral neck during stimulation of single-leg stance. On the proximal femur the deformation pattern remained similar to that of the unoperated femurs. The small increase of strains in the neck area alone would probably not be sufficient to cause fracture of the neck However, with patient-related and surgical factors these strain changes may contribute to the risk of early periprosthetic fracture

Conventional non-steroidal anti-inflammatory drugs (NSAIDs) and newer specific cyclo-oxygenase-2 (cox-2) inhibitors are commonly used in musculoskeletal trauma and orthopaedic surgery to reduce the inflammatory response and pain. These drugs have been reported to impair bone metabolism. In reconstruction of the anterior cruciate ligament the hamstring tendons are mainly used as the graft of choice, and a prerequisite for good results is healing of the tendons in the bone tunnel. Many of these patients are routinely given NSAIDs or cox-2 inhibitors, although no studies have elucidated the effects of these drugs on tendon healing in the bone tunnel.

In our study 60 female Wistar rats were randomly allocated into three groups of 20. One received parecoxib, one indometacin and one acted as a control. In all the rats the tendo-Achillis was released proximally from the calf muscles. It was then pulled through a drill hole in the distal tibia and sutured anteriorly. The rats were given parecoxib, indometacin or saline intraperitoneally twice daily for seven days. After 14 days the tendon/bone-tunnel interface was subjected to mechanical testing.

Significantly lower maximum pull-out strength (p < 0.001), energy absorption (p < 0.001) and stiffness (p = 0.035) were found in rats given parecoxib and indometacin compared with the control group, most pronounced with parecoxib.

A total of 20 pairs of fresh-frozen cadaver femurs were assigned to four alignment groups consisting of relative varus (10° and 20°) and relative valgus (10° and 20°), 75 composite femurs of two neck geometries were also used. In both the cadaver and the composite femurs, placing the component in 20° of valgus resulted in a significant increase in load to failure. Placing the component in 10° of valgus had no appreciable effect on increasing the load to failure except in the composite femurs with varus native femoral necks. Specimens in 10° of varus were significantly weaker than the neutrally-aligned specimens.

The results suggest that retention of the intact proximal femoral strength occurs at an implant angulation of ≥ 142°. However, the benefit of extreme valgus alignment may be outweighed in clinical practice by the risk of superior femoral neck notching, which was avoided in this study.