Background and purpose

Bone morphogenic proteins (BMPs) can be used in non-unions to replace autograft. BMPs induce osteoblasts and (less well known) also osteoclasts, which can in turn be controlled by a bisphosphonate. In the present study, our aim was to improve the biological effect of autologous bone graft by adding an anabolic BMP, with or without bisphosphonates, in an open-fracture model prone to non-union.

Methods

Rat femurs were osteotomized and fixed with an intramedullary K-wire. Autograft was placed at the osteotomy, mixed with either saline or BMP-7. After 2 weeks, the rats had a single injection of saline or of a bisphosphonate (zoledronate). The rats were killed after 6 weeks and the femurs were evaluated by radiography, micro-CT, histology, and 3-point bending test.

Results

All fractures healed. The callus volume was doubled in the BMP-treated femurs (p < 0.01) and increased almost 4-fold in the femurs treated with both BMP and systemic zoledronate (p < 0.01) compared to autograft. In mechanical testing, the autograft group reached approximately half the strength of the contralateral, non-osteotomized femur (p < 0.001). By adding BMP to the autograft, the strength was doubled (p < 0.001) and with both BMP and systemic zoledronate, the strength was increased 4-fold (p < 0.001) compared to autograft alone.

Interpretation

The combination of BMP and bisphosphonate as an adjunct to autograft is superior to autograft alone or combined with BMP. The combination may prove valuable in the treatment of non-unions.

Background and purpose

Primary spontaneous osteonecrosis of the knee is a painful lesion in the elderly without any known cause. The onset of pain is usually acute. The prognosis is poor with high frequency of osteoarthritis, joint surface collapse, and subsequent knee surgery. In the present study, we determined whether bisphosphonates can prevent the joint surface collapse by delaying the post-necrotic remodeling.

Patients and methods

Between 2006 and 2009, 17 consecutive patients (mean age 68 years) with clinical and radiographic signs of knee osteonecrosis were identified and given alendronate, 70 mg perorally, once a week for a minimum of 6 months. The patients were followed clinically, radiographically, and by MRI.

Results

10 of the 17 patients did not develop osteoarthritis (group A), 4 patients developed mild osteoarthritis but no knee joint surface collapse (group B), and 3 patients had a joint surface collapse (group C). 2 of the 3 patients in group C—as compared to none in the other groups—stopped medication prematurely, due to side effects.

Interpretation

Compared to a previous, untreated series of osteonecrosis patients at our hospital, the clinical results in the present series appeared better. 59% of the patients had a complete radiographic recovery, as compared to 25% in the original study. 12% were failures regarding need to undergo surgery when bisphosphonates were given, as compared to 32% in the previous untreated series. An anticatabolic drug delaying the remodeling might be an effective treatment in osteonecrosis of the knee but further (preferably randomized) studies are necessary.

Background and purpose

We have previously shown in a randomized study that in the first year after treatment, open reduction and internal fixation resulted in better grip strength and forearm rotation than closed reduction and bridging external fixation. In the present study, we investigated whether this difference persists over time.

Patients and methods

The 50 patients included in the original study (mean age 53 years, 36 women) were sent a QuickDASH questionnaire and an invitation to a radiographic and clinical examination after a mean of 5 (3–7) years.

Results

All 50 patients returned the QuickDASH questionnaire and 45 participated in the clinical and radiographic examination. In the internal fixation group, the grip strength was 95% (SD 12) of the uninjured side and in the external fixation group it was 90% (SD 21) of the uninjured side (p = 0.3). QuickDASH score, range of motion, and radiographic parameters were similar between the groups.

Interpretation

The difference originally found between internal and external fixation in distal radial fractures at 1 year regarding grip strength and range of motion was found to diminish with time. At 5 years, both groups had approached normal values.

Background

Bisphosphonates increase the callus size and strength in animal fracture studies. In a human non-randomized pilot study of high tibial osteotomies in knee osteoarthritis, using the hemicallotasis (HCO) technique, bisphosphonates shortened the healing time by 12 days. In the present randomized study, we wanted to determine whether a single infusion of zoledronic acid reduces the time to clinical osteotomy healing. Results from the same trial, showing improved pin fixation with zoledronate, have been published separately.

Methods

46 consecutive patients (aged 35–65 years) were operated. At 4 weeks postoperatively, the patients were randomized to an intravenous infusion of either zoledronic acid or sodium chloride. Dual-energy X-ray absorptiometry (DEXA) was performed 10 weeks postoperatively. Radiographs were taken at 10 weeks and every second week until there was radiographic and clinical healing. Healing was evaluated blind, with extraction of the external fixator as the endpoint. At 1.5 years, an additional radiograph was taken and the hip-knee-ankle (HKA) angle measured to evaluate whether correction had been retained.

Results

All osteotomies healed with no difference in healing time between the groups (77 (SD 7) days). Bone mineral density and bone mineral content, as assessed with DEXA, were similar between the groups. Radiographically, both groups had retained the acquired correction at the 1.5-year follow-up.

Interpretation

In this randomized comparison, a single infusion of zoledronic acid increased the pin fixation of the external frame but did not shorten the healing time. In both groups, the external fixator was extracted almost 2 weeks earlier than in previous studies. The early extraction did not cause a loss of correction in either group.

Background and purpose

The remodeling of morselized bone grafts in revision surgery can be enhanced by an anabolic substance such as a bone morphogenetic protein (BMP). On the other hand, BMPs boost catabolism and might cause a premature resorption, both of the graft and of the new-formed bone. Bisphosphonates inactivate osteoclasts and can be used to control the resorption. We studied a combination of both drugs as a local admix to a cancellous allograft.

Methods

Cancellous bone allografts were harvested and freeze-dried. Either saline, BMP-7, the bisphosphonate zoledronate, or a combination of BMP-7 and zoledronate were added in solution. The grafts were placed in bone conduction chambers and implanted in the proximal tibia of 34 rats. The grafts were harvested after 6 weeks and evaluated by histomorphometry.

Results

Bone volume/total volume (BV/TV) was 50% in the grafts treated with the combination of BMP-7 and zoledronate and 16% in the saline controls (p < 0.001). In the zoledronate group BV/TV was 56%, and in the BMP group it was 14%. The ingrowth distance of new bone into the graft was 3.5 mm for the combination of BMP-7 and zoledronate and 2.6 mm in the saline control (p = 0.002). The net amount of retained remodeled bone was more than 4 times higher when BMP-7 and zoledronate were combined than in the controls.

Interpretation

An anabolic drug like BMP-7 can be combined with an anti-catabolic bisphosphonate as local bone graft adjunct, and the combination increases the amount of remaining bone after remodeling is complete.

Background and purpose In unstable distal radial fractures that are impossible to reduce or to maintain in reduced position, the treatment of choice is operation. The type of operation and the choice of implant, however, is a matter of discussion. Our aim was to investigate whether open reduction and internal fixation would produce a better result than traditional external fixation.

Methods 50 patients with an unstable or comminute distal radius fracture were randomized to either closed reduction and bridging external fixation, or open reduction and internal fixation using the TriMed system. The primary outcome parameter was grip strength, but the patients were followed for 1 year with objective clinical assessment, subjective outcome using DASH, and radiographic examination.

Results At 1 year postoperatively, grip strength was 90% (SD 16) of the uninjured side in the internal fixation group and 78% (17) in the external fixation group. Pronation/supination was 150° (15) in the internal fixation group and 136° (20) in the external fixation group at 1 year. There were no differences in DASH scores or in radiographic parameters. 5 patients in the external fixation group were reoperated due to malunion, as compared to 1 in the internal fixation group. 7 other cases were classified as radiographic malunion: 5 in the external fixation group and 2 in the internal fixation group.

Interpretation Internal fixation gave better grip strength and a better range of motion at 1 year, and tended to have less malunions than external fixation. No difference could be found regarding subjective outcome.