Intractable Fractures of the Bilateral Proximal Ulnae After 8 Years of Zoledronate Treatment for Breast Cancer Bone Metastasis.

Long-term administration of bisphosphonates strongly suppresses osteoclastic bone resorption and rarely causes atypical fractures. This report presents a case of bilateral atypical ulnar fractures, following an 8-year course of zoledronate to treat breast cancer bone metastasis. Nonsurgical treatment for the left ulnar fracture failed, in spite of minimal displacement with callus formation at initial presentation. After failure of plate fixation with a pedicled vascularized bone graft, removal of osteosclerotic lesions and plate fixation with corticocancellous iliac bone graft resulted in bone healing, although the healing process took 1.5 years. Plate fixation for the contralateral fractured ulna was unsuccessful.

Single injection of PTH improves osteoclastic parameters of remodeling at a stress fracture site in rats.

Stress fractures (SFx) result from repetitive cyclical loading of bone. They are frequent athletic injuries and underlie atypical femoral fractures following long-term bisphosphonate (BP) therapy. We investigated the effect of a single PTH injection on the healing of SFx in the rat ulna. SFx was induced in 120 female Wistar rats (300 ± 15 g) during a single loading session. A single PTH (8 µg.100g-1 ) or vehicle (VEH) saline injection was administered 24 h after loading. Rats were divided into four groups (n = 15) and ulnae were examined 1, 2, 6, or 10 weeks following SFx. Two Toluidine Blue and TRAP-stained sections of the SFx were examined for histomorphometric analysis using Osteomeasure™ software. An increase in osteoclast number (N.Oc) and perimeter (Oc.Pm) was observed two weeks following PTH treatment (p < 0.01). At 6 weeks, bone formation was the main activity in BMUs. At 10 weeks, the proportion of healing along the SFx line remained 50% greater in PTH groups (p = 0.839), leading to a 43% reduction in the porosity area of BMU (p = 0.703). The main effect of time was a significant variable along the entire SFx remodeling cycle, with significant interactions between time and treatment type affecting (N.Oc) (p = 0.047) and (Oc.Pm) (p = 0.002). We conclude that a single PTH injection increases osteoclastogenesis by the second week of the remodeling cycle in a SFx in vivo. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Intravenous regional anaesthesia (Bier's block) for pediatric forearm fractures in a pediatric emergency department-Experience from 2003 to 2014.

STUDY OBJECTIVES: To evaluate the efficacy (length of stay in the emergency department and failure rate of Bier's block) and safety profile (death and major complications) of Bier's block in its use for manipulation and reduction of paediatric forearm fractures. METHODS: This is a retrospective cohort study of pediatric patients in KKWomen's and Children's Hospital Children's Emergency Department with forearm fractures between Jan 2003 and Dec 2014 who underwent manipulation and reduction using Bier's block. Demographic data, time from registration to discharge, major complications and success rate were collated in a standardized data collection form. A subanalysis of the Bier's block group from 2009 to 2014 was performed and compared to a corresponding data set of paediatric patients who underwent manipulation and reduction of forearm fractures using ketamine for procedural sedation from 2009 to 2014. RESULTS: 1781 cases of paediatric forearm fractures were analysed. The mean age of patients in the Bier's block group was 12.0 years (range 5.5-17.8 years old). Of all patients undergoing Bier's block, 1471 out of 1781 patients were male (82.7%). The mean length of stay (LOS) in the department was 168±72min, measured from time of registration till departure. From our subanalysis of data from 2009 to 2014, the mean LOS for the Bier's block group was shorter - 170min compared to 238min for the ketamine group (P <0.0001). 2 patients had failed Bier's block which required a repeat procedural sedation using ketamine. 96% of patients who underwent Bier's block were discharged with an outpatient orthopaedic appointment. There were no deaths or major complications identified in our study. CONCLUSION: Bier's block is a safe technique for reduction of fractures when used in the appropriate population and fracture types, with a low failure rate and no major complications including death. Compared to the ketamine group, it has a shorter length of stay in the emergency department. We recommend the adoption of this practice for manipulation and reduction of pediatric forearm fractures in the Emergency Department with a formalised protocol to reduce and prevent any human errors that can potentially result in complications.

Treatment of Infected Forearm Nonunions With Large Complete Segmental Defects Using Bulk Allograft and Intramedullary Fixation.

PURPOSE: The purpose of this study is to report the results of a series of infected forearm nonunions treated from 1998 to 2012 using a staged reconstruction technique. METHODS: At a median of 42 months follow-up, 7 patients who had an average segmental defect of 4.9 cm (range, 2.3-10.4 cm) were available for clinical and radiographic evaluation. Treatment consisted of serial debridement, implantation of an antibiotic cement spacer, and staged reconstruction using a bulk radius or ulna allograft with intramedullary fixation. RESULTS: All 7 patients ultimately achieved solid bone union, although 4 patients (57%) required additional surgery, consisting of autologous bone grafting and plating, to achieve healing at 1 of the allograft-host junction sites. No patient had recurrence of infection, and all reported substantial improvement with increased function and decreased pain. CONCLUSIONS: Our approach ultimately resulted in a 100% union rate without recurrence of infection, although many patients may require additional surgery to attain healing at both allograft-junction sites. Using bulk allograft provides the ability to span a large defect while reconstituting the forearm anatomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

The effect of strontium ranelate on the healing of a fractured ulna with bone gap in rabbit.

BACKGROUND: Fracture healing in bone gap is one of the major challenges encountered in Orthopedic Surgery. At present, the treatment includes bone graft, employing either internal or external fixation which has a significant impact on the patient, family and even society. New drugs are emerging in the markets such as anabolic bone-forming agents including teriparatide and strontium ranelate to stimulate bone growth. Based on the mechanism of their actions, we embarked on a study on the healing of a fractured ulna with bone gap in a rabbit model. We segregated ten rabbits into two groups: five rabbits in the test group and five rabbits in the control group. We created a 5 mm bone gap in the ulna bone, removing the periosteum as well. Rabbits in the test group received 450 mg/kg of strontium ranelate via oral administration, daily, for six weeks. The x-rays, CT scans and blood tests were performed every two weeks. At the end of six weeks, the rabbits were sacrificed, and the radius and ulna bones harvested for histopathological examination. RESULTS: Based on the x-rays and CT scans, fracture healing or bone formation was observed to be faster in the control group. From the x-ray findings, 80 % of the fracture united and by CT scan, 60 % of the fracture united in the control group at the end of the six-week study. None of the fractures united in the test group. However, the histopathology report showed that a callus of different stages was being formed in both groups, consisting of 80 % of bone. The serum levels of osteocalcin and alkaline phosphatase initially remained similar up to three weeks and changed slightly at the end of six weeks. CONCLUSIONS: We conclude that the strontium effect begins slowly, and while it may not interfere with bone cell proliferation it may interfere in the mineralization and delay the acute stage of fracture healing. We recommend that a larger sample size and a longer duration of the study period be implemented to confirm our finding.

The effect of rhBMP-2 in a novel, non-instrumented extremity nonunion model.

BACKGROUND: Pre-clinical models of bony nonunion typically employ critical-length defects. However, these models may not accurately reflect clinical practice since many nonunions are diagnosed without bone loss. We developed a non-displaced rat ulna fracture model in order to examine the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with an absorbable collagen sponge (ACS) for nonunion treatment. METHODS: Transverse diaphyseal ulna fractures were created in 24 Sprague-Dawley rats. Eight animals (Group 1: Nonunion) received no further intervention. The remaining 16 animals were treated with 5 µg rhBMP-2/ACS at 8 weeks after the original intervention (Group 2: Nonunion + BMP) or at the time of initial injury (Group 3: Fresh fracture + BMP). RESULTS: In Group 1, 7 of 8 fractures demonstrated gross motion and a persistent radiographic gap (12.5% healing rate). In Groups 2 and 3, fractures healed at a rate of 75% (6 of 8 in each group) as determined by manual and radiographic evaluation. Biomechanical testing for torque load-to-failure and torsional stiffness demonstrated no significant difference between healed specimens treated with rhBMP-2. CONCLUSIONS: To our knowledge, this is the first description of a physiologic, non-stabilized, non-defect fracture nonunion model in a rodent. Furthermore, unlike previous nonunion models, the healing rates after treatment with rhBMP-2 are comparable to that of clinical data, suggesting that this model may provide an environment more representative of nonunions in humans.

BMP-2 delivered from a self-crosslinkable CaP/hydrogel construct promotes bone regeneration in a critical-size segmental defect model of non-union in dogs.

OBJECTIVES: To determine whether the addition of recombinant human bone morphogenetic protein (rhBMP-2) to a self-crosslinkable cellulosic hydrogel/biphasic calcium phosphate (BCP) granules construct promotes bone healing in critical-size ulnar defects in dogs. METHODS: A standardized 2 cm long ulnar ostectomy was performed bilaterally in five dogs to compare bone healing with hydrogel/BCP constructs associated with or without rhBMP-2. Cancellous-bone autografts were used as positive controls in unilateral ulnar defects in five additional dogs. Radiographically, bone healing was evaluated at four, eight, 12, 16 and 20 weeks postoperatively. Histological qualitative analysis with microCT imaging and light and scanning electron microscopy were performed 20 weeks after implantation. RESULTS: All rhBMP-2-loaded constructs induced the formation of well-differentiated mineralized lamellar bone surrounding the BCP granules and bridging bone/implant interfaces as early as eight weeks after surgery. Bone regeneration appeared to develop earlier with the rhBMP-2 constructs than with the cancellous-bone autografts while similar results were obtained at 20 weeks. Constructs without any rhBMP-2 showed osteoconductive properties limited to the bone junctions and a lack of osteoinduction without bone ingrowth within the implantation site. In one dog, the leakage of the hydrogel loaded with rhBMP-2 induced an extensive heterotopic bone formation. CLINICAL SIGNIFICANCE: The addition of rhBMP-2 to a self-crosslinkable hydrogel/BCP construct could promote bone regeneration in a critical-size-defect model with similar performance to autologous bone grafts.

Weekly teriparatide administration for the treatment of delayed union: a report of two cases.

UNLABELLED: Two cases of delayed union that were effectively treated with weekly TPTD administration are described. The effect of this therapy was observed within 4 weeks. INTRODUCTION: In the first case, a 72-year-old woman underwent osteotomy for the treatment of hallux valgus. Bone union was still not observed 4 months after surgery. Therefore, weekly teriparatide (56.5 mg) injections were administered, resulting in the initiation of bone union within 4 weeks and complete bone union 4 months after the first teriparatide injection. In the second case, a 72-year-old woman underwent open reduction and internal fixation of an olecranon fracture. Bone union was delayed 4 months after surgery; therefore, weekly teriparatide (56.5 mg) injections were started. RESULTS: The initiation of bone union was slightly evident within 4 weeks, and complete healing was achieved 4 months after the first teriparatide injection. In both cases, no serious teriparatide-related adverse effects were observed. CONCLUSION: Weekly teriparatide administration was effective for bone healing and useful for delayed union; moreover, the effect of this therapy showed within 4 weeks.

The use of bone morphogenic protein-7 (OP-1) in the management of resistant non-unions in the upper and lower limb.

The aim of the present study was to investigate the safety and efficacy of local implantation of BMP-7 for the treatment of resistant non-unions in the upper and lower limb. Fifty-two patients (30 males, mean age 52.8 years; range 20-81) were treated with local BMP-7 implantation in a bovine bone-derived collagen paste with or without revision of fixation. Thirty-six patients had closed injuries, ten had open injuries and six had infected non-unions. Patients had undergone a mean of 2 (1-5) operations prior to implantation of BMP-7. Clinical and radiological union was achieved in 94% at a mean time of 5.6 months (3-19). Two patients with subtrochanteric femoral fractures failed to achieve union secondary to inadequate fracture stabilisation, persistent unfavourable biological environment and systemic co-morbidities. One patient developed synostosis attributed to the BMP-7 application. This study demonstrates BMP-7 implanted in a bovine-derived collagen paste is an effective adjunctive treatment for resistant non-unions in the upper and lower limb.

Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects.

Because bone morphogenetic protein 2 gene transfected Escherichia coli (E-BMP-2) produce recombinant human BMP-2 (rhBMP-2) more efficiently than mammalian cells (Chinese hamster ovary [CHO]-BMP-2), they may be a more cost-effective source of rhBMP-2 for clinical use. However, use of E-BMP-2 for regenerating long bones in large animals has not been reported. In the current study, we evaluated the healing efficacy of E-BMP-2 in a canine model. We created 2.5-cm critical-size segmental ulnar defects in test animals, then implanted E-BMP-2 and 700 mg of artificial bone (beta-tricalcium phosphate; ß-TCP) into the wounds. We examined the differential effects of 5 E-BMP-2 treatments (0, 35, 140, 560, and 2240 µg) across 5 experimental groups (control, BMP35, BMP140, BMP560, and BMP2240). Radiography and computed tomography were used to observe the regeneration process. The groups in which higher doses of E-BMP-2 were administered (BMP560 and BMP2240) displayed more pronounced bone regeneration; the regenerated tissues connected to the host bone, and the cross-sectional areas of the regenerated bone were larger than those of the originals. The groups in which lower doses of E-BMP-2 were administered (BMP35 and BMP140) experienced relatively less bone regeneration; furthermore, the regenerated tissues failed to connect to the host bone. In these groups, the cross-sectional areas of the regenerated bone were equal to or smaller than those of the originals. No regeneration was observed in the control group. These findings suggest that, like CHO-BMP-2, E-BMP-2 can be used for the regeneration of large defects in long bones and that its clinical use might decrease the cost of bone regeneration treatments.

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna.

Because bisphosphonates (BPs) are potent inhibitors of bone resorption, we hypothesized that they would retard direct remodeling of stress fractures. The aim of this study was to determine the effect of risedronate on direct remodeling and woven bone callus formation following stress fracture formation in the rat ulna. In 135 adult female Wistar rats, cyclic loading of the ulna created stress fractures. Rats were treated daily with oral saline, or risedronate at 0.1 or 1.0 mg/kg. From each bone, histomorphometry was performed on sections stained with toluidine blue at a standard level along the fracture. The high dose of risedronate caused a significant decrease in the percentage of repaired stress fracture and bone resorption along the stress fracture line at 6 and 10 weeks after loading (p < 0.05). At this dose, intracortical resorption was significantly reduced at 10 weeks after loading and intracortical new bone area was significantly reduced at 6 and 10 weeks. Woven bone formation and consolidation phases of stress fracture repair were not affected by low or high doses of risedronate. In conclusion, high dose bisphosphonate treatment impaired healing of a large stress fracture line by reducing the volume of bone resorbed and replaced during remodeling. We also confirmed that periosteal callus formation was not adversely affected by risedronate treatment.

Can low doses of simvastatin enhance fracture healing? An experimental study in rabbits.

Several observational and experimental studies have investigated the potential anabolic effects of statins on undisturbed bone but only a few recent studies have examined the effect of statins on skeletal repair. The goal of the study is to investigate any potential early anabolic effect of the systemic administration of simvastatin in low doses (based on earlier safety and efficacy studies on undisturbed bone) on fracture healing. Fifty-four skeletally mature male New Zealand White rabbits were used for the study. The rabbits were assigned to one of three experimental groups: a control group, and two groups that were orally administrated a diet with 10 and 30 mg/kg/day of simvastatin, respectively. A complete biochemical blood count was performed to exclude drug-induced complications. Half of the animals of each group were sacrificed at 15 days and the other half at 30 days after surgery at which time intervals healing quality was assessed. The bones were subjected to biomechanical testing, histomorphometric analysis and peripheral quantitative computed tomography. In animals received simvastatin of 30 mg/kg/day a significant reduction of BMD, stiffness, and energy absorbed to failure were observed. At 15 days, the amount of cartilaginous callus formation was reduced, and the void space was significantly increased, in the animals of both groups that received simvastatin when compared to the control group (p<.05). Our results suggest that simvastatin doses of 30 mg/kg/day may have a negative anabolic effect on callus formation in rabbits, whereas doses of 10 mg/kg/day seem not to produce a significant positive or a negative effect, especially at the early stages of fracture remodeling.

[Modern approach to the rehabilitation of children with fractured long tubular bones].

An optimized therapeutic rehabilitation program involved 393 patients with fractured long bones (humeral, radial/ulnar, femoral, crural) admitted to the Orthopedic Department of the Stavropol Regional Children's Clinical Hospital and the Rehabilitation Centre for Handicapped Children and Adolescents. Rehabilitation was performed in three consecutive stages, viz. immobilization, functional recovery and training. The proposed approach ensured rather fast functional recovery of the affected extremity even in cases with compound fractures. The rehabilitation program included polyenzyme therapy with wobenzym during 3-4 weeks after injury or surgical repositioning of bone fragments. Pain and oedema syndromes resolved twice as fast as after traditional treatment. The use of this program permitted to avoid development of contracture and disturbances of locomotary activity; moreover, it improved the quality of life in children with fractures of long tubular bones.

Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomised clinical study on 120 patients.

The purpose of this prospective randomised clinical study was to compare the efficacy of recombinant bone morphogenetic protein 7 (rhBMP-7) and platelet-rich plasma (PRP) as bone-stimulating agents in the treatment of persistent fracture non-unions. One hundred and twenty patients were randomised into two treatment groups (group rhBMP-7 vs. group PRP). Sixty patients with sixty fracture non-unions were assigned to each group (median age: 44 years, range 19-65, for the rhBMP-7 group and 41 years, range 21-62, for the PRP group, respectively). In the rhBMP-7 group, there were 15 tibial non-unions, 10 femoral, 15 humeral, 12 ulnar, and 8 radial non-unions. In the PRP group, there were 19 tibial non-unions, 8 femoral, 16 humeral, 8 ulnar, and 9 radial non-unions. The median number of operations performed prior to our intervention was 2 (range 1-5) and 2 (range 1-5) with autologous bone graft being used in 23 and 21 cases for the rhBMP-7 and PRP groups, respectively. Both clinical and radiological union occurred in 52 (86.7%) cases of the rhBMP-7 group compared to 41 (68.3%) cases of the PRP group, with a lower median clinical and radiographic healing time observed in the rhBMP-7 group (3.5 months vs. 4 months and 8 months vs. 9 months, respectively). This study supports the view that in the treatment of persistent long bone non-unions, the application of rhBMP-7 as a bone-stimulating agent is superior compared to that of PRP with regard to their clinical and radiological efficacy.

Improved healing efficacy in canine ulnar segmental defects with increasing recombinant human bone morphogenetic protein-2/allograft ratios.

OBJECTIVES: A validated canine critical-sized segmental defect model was used to compare efficacy of volumetric ratios of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) with cancellous allograft bone or biphasic calcium phosphate ceramic granules using radiographic, biomechanical, and histologic analyses. METHODS: Eighteen mixed-breed hounds received bilateral critical-sized ulnar segmental defects. The six treatment groups included 1:5, 1:2, and 1:1 volumetric ratios of rhBMP-2/ACS to cancellous allograft chips; a 1:1 volumetric ratio of rhBMP-2/ACS to biphasic calcium phosphate ceramic granules; iliac crest autograft alone; and cancellous allograft chips alone (n = 6 ulna per group). Animals were euthanized at 12 weeks and analyzed by radiography, torsion testing, and histology. RESULTS: rhBMP-2/ACS groups demonstrated higher radiographic union than autograft or allograft at 12 weeks. Both treatment groups receiving a 1:1 ratio demonstrated union rates of 100% (12/12 ulna) compared with 17% (1/6) and 0% (0/6) for autograft and allograft, respectively. Torsion testing to failure demonstrated significant increases in maximum torque for all rhBMP-2 groups compared with autograft, but no differences between the rhBMP-2 groups. Ulnae treated with the 1:1 volume ratio of rhBMP-2/ACS to ceramic had the highest histologic union grades followed by 1:1 and 1:2 volume ratios of rhBMP-2/ACS to allograft. CONCLUSIONS: In this study, efficacy of the treatment correlated with the ratio of rhBMP-2/ACS to allograft. As volume of rhBMP-2/ACS decreased below a 1:1 volume ratio, the overall efficacy decreased, thus indicating a potential limit to extending rhBMP-2/ACS past a 1:1 volumetric ratio in large segmental defects. Furthermore, ceramic was found to be a successful replacement for cancellous allograft bone at a 1:1 volumetric ratio. Clinical application using graft expanders or bone void fillers with rhBMP-2 should be used carefully and requires further investigation.

Treatment with rhBMP-2 of extreme radial bone atrophy secondary to fracture management in an Italian Greyhound.

rhBMP-2 solution on a collagen sponge was placed along the diaphysis of an atrophicradius, which had a history of recurring fractures. Two months after rhBMP-2 treatment, new mineralized bone was present, which significantly increased the diameter of the radius and allowed the removal of the external skeletal fixator (ESF). Due to carpo-metacarpal joint compromise, a pancarpal arthrodesis was performed seven months later. At follow-up evaluation two years later the dog was only very mildly lame.

Low-intensity pulsed ultrasound and nonsteroidal anti-inflammatory drugs have opposing effects during stress fracture repair.

Low-intensity pulsed ultrasound (LIPUS) and nonsteroidal anti-inflammatory drugs (NSAIDs) were used to treat stress fracture. Bilateral stress fractures were induced in the ulnas of 48 adult rats. Animals were divided into two groups (NSAID and VEH), and treated 5 days per week with celecoxib (5 mg/kg) mixed in a vehicle solution of polyethylene glycol and saline (NSAID) or vehicle alone (VEH). One-to-three hours following drug administration, all animals were treated with unilateral active-LIPUS and contralateral inactive-LIPUS. Equal numbers of ulnas from each drug group were histologically evaluated at 2, 4, and 8 weeks following induction of stress fracture. Neither LIPUS nor NSAID influenced bone resorption, but each had significant and opposite effects on intracortical bone formation rate. These effects indicate that LIPUS may be used to facilitate stress fracture repair whereas NSAID may delay tissue level repair of stress fractures. There was no interaction between LIPUS and NSAID, indicating that the beneficial LIPUS effect was not mediated by the cyclooxygenase-2 pathway. LIPUS accelerated stress fracture healing, whereas the NSAID delayed repair. When used in combination, the beneficial LIPUS effect was not impaired by the detrimental NSAID effect.

Growth hormone stimulates bone healing in a critical-sized bone defect model.

Growth hormone plays an important role in bone metabolism. Treating bone deficits is a major topic in orthopaedic surgery. Our hypothesis was that local continuous growth hormone administration stimulates bone healing in a canine critical-sized bone defect model. Bone formation in the defects was quantified using densitometric image analysis and histomorphometry. After growth hormone treatment, expression levels of insulin-like growth factors-I and II, and growth hormone receptor were determined in the bone regenerate of the original defects. Circulating plasma concentrations of insulin-like growth factors-I and II, and insulin- like growth factor binding proteins-4, and 6 were measured during treatment. Growth hormone administration resulted in healing of bone defects but without an additional effect of local infusion. Expression of insulin-like growth factor-I in the bone regenerate was lower in the growth hormone-treated dogs, whereas insulin-like growth factor-II and growth hormone receptor expression were not increased. Growth hormone increased circulating insulin-like growth factor-I and growth factor-II plasma concentrations. Continuous infusion of growth hormone stimulated bone healing in a canine critical-sized bone defect model. Local delivery of growth hormone did not additionally enhance bone healing. Increased circulating plasma concentrations of insulin-like growth factors-I and II most likely induced bone formation.

Application of recombinant BMP-7 on persistent upper and lower limb non-unions.

The purpose of this study was to evaluate the efficacy and safety of recombinant bone morphogenetic protein 7 (rhBMP-7 or OP-1) as a bone-stimulating agent in the treatment of persistent fracture non-unions. Twenty-five consecutive patients [19 males, mean age 39.4 years (range: 18-79)] with 26 fracture non-unions were treated with rhBMP-7. There were 10 tibial non-unions, eight femoral, three humeral, three ulnar, one patellar, and one clavicular non-union. The mean follow-up was 15.3 months. The mean number of operations performed prior to rhBMP-7 application was 3.2, with autologous bone graft and bone marrow injection being used in 10 cases (38.5%). Both clinical and radiological union occurred in 24 (92.3%) cases, within a mean time of 4.2 months and 5.6 months, respectively. Of the remaining two cases, one patient ultimately underwent a below knee amputation, secondary to recurrence of deep sepsis. The other patient with recalcitrant ulnar non-union although the radiological union was incomplete, declined further intervention, as he was asymptomatic. No complications or adverse effects from the use of rhBMP-7 were encountered. This study supports the view that the application of rhBMP-7 as a bone-stimulating agent is safe and a power adjunct to be considered in the surgeon's armamentarium for the treatment of these challenging clinical conditions.

rhBMP-2 injected in a calcium phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model.

This study evaluated the ability of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate carrier (alpha-BSM) to accelerate healing in a rabbit ulna osteotomy model compared to untreated surgical controls. Healing was assessed by radiography, histology and biomechanics. Bilateral mid-ulnar osteotomies were created in 16 skeletally mature rabbits. One limb in each animal was injected with either 0.1 mg rhBMP-2/alpha-BSM (BMP) (N=8) or buffer/alpha-BSM (BSM) (N=8). Contralateral osteotomies served as untreated surgical controls (SXCT). Gamma scintigraphy showed 75%, 45% and 5% of the initial 125I-rhBMP-2 dose was retained at the osteotomy site at 3 h, 1 week and 3 weeks. The biological activity of rhBMP-2 (alkaline phosphatase activity from bioassay) extracted from alpha-BSM incubated in vitro up to 30 days at 37 degrees C was unchanged. Radiographs demonstrated complete bridging of the BMP limbs at 4 weeks whereas none of the BSM or SXCT limbs were bridged. Post-mortem peripheral quantitative computed tomography determined mineralized callus area was 62% greater in BMP limbs compared to SXCT limbs. Torsional stiffness and strength were 63% and 103% greater in BMP limbs compared to SXCT limbs. There was no difference in torsional properties between BSM and SXCT limbs. Failure occurred outside the osteotomy in four out of seven of the BMP limbs. All BSM and SXCT limbs failed through the osteotomy. Histology showed bony bridging of the osteotomy and no residual carrier in the BMP limbs. BSM and SXCT groups showed less mature calluses composed of primarily fibrocartilaginous tissue and immature bone in the osteotomy gap. These data indicate rhBMP-2 delivered in alpha-BSM accelerated healing in a rabbit ulna osteotomy model compared to BSM and SXCT groups.