Sclerostin is a negative regulator of osteoblast differentiation and bone formation. Expressed by osteocytes, it acts through antagonising the Wnt/â-catenin pathway and/or BMP activity. Distraction osteogenesis, used for limb lengthening and reconstruction, can be complicated by disuse osteopenia and poor healing response, both of which would benefit from pro anabolic therapy.

We examined the effects of Sclerostin Antibody (Scl-AbIII, Amgen Inc.,) in a rat model of distraction osteogenesis. A femoral osteotomy was stabilized with an external fixator in male Sprague Dawley rats. After a week of latency, the gap was distracted twice daily for 14 days to a total of 7 mm. Saline or Scl-Ab was administered twice weekly throughout the distraction period and up to 4, 6 or 8 weeks post commencement of distraction. Three groups were examined: Saline, Continuous Scl-Ab throughout the study (C Scl-Ab), and Delayed Scl-Ab with commencement of Scl-Ab after distraction (D Scl-Ab).

Regenerate bone mineral content (BMC), determined by DEXA, was increased 36% at 4 weeks and 86% at 6 weeks with C Scl-Ab, resulting in a 65% increase in bone mineral density (BMD) at 6 weeks, compared with Saline (p<0.01). D Scl-Ab treatment showed a 41% increase in BMC and a 31% increase in BMD compared with Saline at 6 weeks (p<0.05). At 8 weeks, C Scl-Ab remained significantly increased over Saline (72% in BMC; 60% in BMD).

Micro-CT scans of the regenerate revealed increases in bone volume of 88% with C Scl Ab and 65% with D Scl-Ab compared with Saline at 6 weeks (p<0.05). By 8 weeks, these increases were 36% for C Scl-Ab (p<0.05) and 37% for D Scl-Ab compared with Saline (p<0.01). Importantly, mean moment of inertia was increased over two-fold in both Scl-Ab groups at 6 weeks compared with Saline (p<0.05). Histology at 6 weeks confirmed micro-CT data with 85–88% increases in bone volume/tissue volume (BV/TV) in the regenerate with both C Scl-Ab and D Scl-Ab compared with Saline (p<0.05). Analysis of bone formation at 6 weeks revealed increases in mineral apposition rate of 56% in C Scl-Ab and 52% in D Scl-Ab compared with Saline (p<0.05).

Scl-Ab treatment increased bone formation in this model of distraction osteogenesis, resulting in a larger regenerate callus (increased BMC and BV/TV). We expect further studies to reveal increases in mechanical strength. Scl-Ab may hold promise as a therapeutic to accelerate regenerate formation and consolidation in distraction osteogenesis for limb reconstruction.

Developing biomaterials for bone regeneration that are highly bioactive, resorbable and mechanically strong remains a challenge. Zreiqat's lab recently developed novel scaffolds through the controlled substitution of strontium (Sr) and zinc (Zn) into calcium silicate, to form Sr-Hardystonite and Hardystonite, respectively and investigated their in vivo biocompatibility and osteoconductivity

We synthesized 3D scaffolds of Sr-Hardystonite, Hardystonite and compared them to the clinically used tricalcium phosphate (micro-TCP) (6 × 6 × 6 mm) using a polyurethane foam template to produce a porous scaffold. The scaffolds were surgically implanted in the proximal tibial metaphysis of each tibia of Female Wistar rats. Animals were sacrificed at three weeks and six weeks post-implantation and bone formation and scaffold resorption were assessed by microcomputed tomography (micro-CT) histomorphometry and histology. Histological staining on undecalcified sections included Toluidine blue, tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP).

The bone formation rate and mineral apposition rate will be determined by analysing the extent and separation of fluorescent markers by fluorescent microscopy micro-CT results revealed higher resorbability of the developed scaffolds (Sr-Hardystonite and Hardystonite) which was more pronounced with the Sr-Hardystonite. Toluidine blue staining revealed that the developed ceramics were well tolerated with no signs of rejection, necrosis, or infection. At three weeks post implantation, apparent bone formation was evident both at the periphery and within the pores of the all the scaffolds tested. Bone filled in the pores of the Sr- Hardystonite and Hardystonite scaffolds and was in close contact with the ceramic. In contrast, the control scaffolds showed more limited bone ingrowth and a cellular layer separating the ceramic scaffolds from the bone. By six weeks the Hardystonite and Sr Hardystonite scaffolds were integrated with the bone with most pores filled with new bone. The control scaffold showed new bone formation in the plane of the cortical bone but little new bone where the scaffold entered the marrow space. Sr Hardystonite showed the greatest resorbability with replacement of the ceramic material by bone.

We have developed novel engineered scaffolds (Sr-Hardystonite) for bone tissue regeneration. The developed scaffolds resorbed faster than the clinically used micro- TCP with greater amount of bone formation replacing the resorbed scaffold.

Background: Recombinant bone morphogenic proteins (BMPs) are potent bone anabolic agents suggested for the treatment of orthopaedic complications associated with neurofibromatosis type 1 (NF1), in particular, congenital pseudarthrosis of the tibia. We have explored the effect of Nf1 haploinsufficiency on ex vivo and in vivo models of BMP-induced bone formation in Nf1+/− mice.

Methods: Using an Nf1+/− knockout mouse model, we expanded primary cell cultures from calvarial and long bone osteoblasts and measured osteogenic markers, such as alkaline phosphatase and mineralization using Alizarin Red staining, and the responses of these markers to BMP-2 treatment. We also developed an in vivo muscle pouch heterotopic ossification model to assess the ability of BMP-2 to form bone.

Results: Primary osteoblast cultures from Nf1+/− mice showed reduced ALP staining, ALP activity and mineralization, denoting an anabolic deficiency. Nf1+/− osteoblasts responded to BMP-2 treatment, although osteogenic markers were reduced compared to BMP-2 treated Nf1+/+osteoblasts. Heterotopic bone was induced in both genotypes by surgically implanting BMP-2, however less bone was formed in Nf1+/− mice than Nf1+/+ controls.

Conclusion: These data indicate that BMP therapies have potential utility in treating orthopaedic defects in children with NF1, but that dosing may need to be optimized for this patient subgroup or that catabolism may need to be also controlled.

To determine whether HIV seropositivity is a significant risk factor for infection following open fractures of long bones, we undertook a prospective cohort-type analytical study.

We obtained Ethics Committee approval and invited suitable patients (adults with open fractures of long bones) presenting to our institution to participate in the study. Written informed consent was obtained and the patient registered. Baseline blood tests were done (Hb, HIV, Albumin, CD4 count), after which treatment proceeded in the standard manner. At set intervals, patient records were accessed and information captured in a database. Patients were followed up until bony union had occurred.

To date, 50 patients have been recruited to the study. Of these, 19 were followed up until bony union. All but one of these patients was male and the mean age was 34.5 years. Fractures included three femora, two humeri, two radii and 15 tibiae. There were five Gustilo-Anderson grade-I, seven grade-II, six grade-IIIa and three grade-IIIb open fractures. Three of the 19 patients tested positive for HIV (15.8%). Infection occurred in five patients (26.3%), none of whom was HIV-positive. The strongest predictor for infection was the time delay to wound inspection, with mean delays of 56.9 hours and 100.2 hours respectively in patients who did and did not develop infection.

Although our study is small, it suggests that asymptomatic HIV seropositivity is not a significant risk factor for infection following open fractures of long bones. Delayed wound inspection puts patients at increased risk.