Teriparatide improves early callus formation in distal radial fractures: Analysis of a subgroup of patients within a randomized trial

Background Teriparatide (parathyreoid hormone; PTH 1-34) increases skeletal mass in humans and improves fracture healing in animals. A recent randomized multicenter trial of nonoperated distal radial fractures showed a moderate shortening of the time to restoration of cortical continuity by treatment with 20 μg (low-dose) teriparatide per day, but not with 40 μg (high-dose). As radiographic cortical continuity appears late in the healing process, perhaps too late for clinical relevance, we studied the qualitative appearance of the callus 5 weeks after fracture

Osteoporosis : the emperor has no clothes

Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed. PathophysiologyMost fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty. ScreeningCurrently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture. TreatmentThe evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65-80years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20-25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment.Peer reviewe

An approximate model for cancellous bone screw fixation

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Taylor & Francis.This paper presents a finite element (FE) model to identify parameters that affect the performance of an improved cancellous bone screw fixation technique, and hence potentially improve fracture treatment. In cancellous bone of low apparent density, it can be difficult to achieve adequate screw fixation and hence provide stable fracture fixation that enables bone healing. Data from predictive FE models indicate that cements can have a significant potential to improve screw holding power in cancellous bone. These FE models are used to demonstrate the key parameters that determine pull-out strength in a variety of screw, bone and cement set-ups, and to compare the effectiveness of different configurations. The paper concludes that significant advantages, up to an order of magnitude, in screw pull-out strength in cancellous bone might be gained by the appropriate use of a currently approved calcium phosphate cement

Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density: A bone chamber study in rats

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

Wnt signaling and orthopedics, an overview

Wnt signaling is a ubiquitous system for intercellular communication, with multiple functions during development and in homeostasis of the body. It comprises several ligands, receptors, and inhibitors. Some molecules, such as sclerostin, appear to have bone-specific functions, and can be targeted by potential drugs. Now, ongoing clinical trials are testing these drugs as treatments for osteoporosis. Animal studies have also suggested that these drugs can accelerate fracture healing and implant fixation. This brief overview focuses on currently available information on the effects of manipulations of Wnt signaling on bone healing

Biological effects of rinsing morsellised bone grafts before and after impaction

Rinsing bone grafts before or both before and after impaction might have different effects on the incorporation of the graft. Rinsing again after impaction might negatively influence bone induction if growth factors released by impaction are washed away. We studied if transforming growth factor-βs (TGF-βs) and bone morphogenetic proteins (BMPs) are released from the mineralised matrix by impaction and if these released growth factors induce osteogenic differentiation in human mesenchymal stem cells (hMSCs). Rinsed morsellised bone allografts were impacted in a cylinder and the escaping fluid was collected. The fluid was analysed for the presence of TGF-βs and BMPs, and the osteoinductive capacity was tested on hMSCs. Abundant TGF-β was present in the fluid. No BMPs could be detected. Osteogenic differentiation of hMSCs was inhibited by the fluid. Results from our study leave us only able to speculate whether rinsing grafts again after impaction has a beneficial effect on the incorporation process or not

Mechanical properties during healing of Achilles tendon ruptures to predict final outcome: A pilot Roentgen stereophotogrammetric analysis in 10 patients

<p>Abstract</p> <p>Background</p> <p>There are presently few methods described for in vivo monitoring of the mechanics of healing human tendon ruptures, and no methods for prediction of clinical outcome. We tested if Roentgen stereophotogrammetric analysis (RSA) can be used to follow the restoration of mechanical properties during healing of ruptured Achilles tendons, and if early measurements can predict clinical results.</p> <p>Methods</p> <p>Achilles tendon repair was studied with RSA in 10 patients with a total rupture. Tantalum beads were implanted in conjunction with surgical repair. The patients were evaluated at 6, 12 and 18 weeks, and after 1 year. RSA was performed with two different mechanical loadings, and the strain induced by increasing load was measured. The transverse area was determined by ultrasound. CT scan at 12 weeks confirmed that the tantalum beads were located within the tendons. Functional testing was done after 1 year. A heel raise index was chosen as primary clinical outcome variable.</p> <p>Results</p> <p>The strain was median 0.90, 0.32 and 0.14 percent per 100 N tendon force at 6 weeks, 18 weeks and one year respectively. The error of measurement was 0.04 percent units at 18 weeks. There was a large variation between patients, which appears to reflect biological variation. From 6 to 18 weeks, there was a negative correlation between increase in transverse area and increase in material properties, suggesting that healing is regulated at the organ level, to maximize stiffness. Modulus of elasticity during this time correlated with a heel raise index at one year (Rho = 0.76; p = 0.02).</p> <p>Conclusion</p> <p>We conclude that the RSA method might have potential for comparing different treatments of Achilles tendon ruptures.</p