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.

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.

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.

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.

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.

[Effects of bone morphogenetic protein and transforming growth fractor-beta on biomechanical property for fracture healing in rabbit ulna].

OBJECTIVE: To investigate the effects of exogenous bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF-beta) on biomechanical property for ulna of fracture healing. METHODS: Thirty-six adult rabbits were made the model of right ulnar fracture and treated locally with TGF-beta/PLA, BMP/PLA, TGF-beta + BMP/PLA or PLA (as control group). Fracture healing was evaluated by measurement of the mechanical parameters and geometric parameters. RESULTS: As compared with control group, the geometric parameters, the bending broken load, the ultimate bending strength, the bending elastic modulus, the ultimate flexural strength, the flexural elastic modulus, the ultimate compressing strength, the compressing elastic modulus, and the ultimate tensile strength for ulna of fracture healing increased significantly in the treatment groups(P < 0.01). These parameters were higher in TGF-beta + BMP/PLA group than in TGF-beta/PLA group or in BMP/PLA group and in TGF-beta/PLA group than in BMP/PLA group(P < 0.05). There was no significant difference in bone density between the treatment groups and control group. CONCLUSION: Local application of exogenous TGF-beta and BMP can increase the callus formation and enhance biomechanical strength of bone after fracture healing. A combination of TGF-beta and BMP has synergetic effect in enhancing fracture healing.

Açäo da calcitonina na resoluçäo de perfuraçöes ósseas em coelhos: controle fotodensitométrio e histológico / Effects of calcitomin in resolution of bone perforations in rabbits: photodensitometric and histogic control

Os autores estudam os efeitos da calcitonina humana sintética (CHS) em perfuraçöes ósseas de ulnas de 13 coelhos, agrupados em uma amostra controle e um grupo tratado com CHS, na dose de 0,34UI (0,34mg) em duas administraçöes diárias por via IM durante 15 dias. Como parâmetros evolutivos utilizaram-se a microfotodensitometria, método destinado a avaliar a densidade óssea das áreas perfuradas, e também a verificaçäo das condiçöes histopatológicas locais após 15 dias de reparaçäo óssea. Os resultados obtidos ressentem-se do pequeno número da amostra; contudo, permitem supor que, através de mecanismos näo inteiramente confirmados, a calcitonina parece ter interferido positivamente na reparaçäo das perfuraçöes ósseas