In our ongoing attempt to identify pharmacologic interventions that improve fracture healing, the sclerostin inhibitor romosozumab is a logical candidate, as it has been shown to decrease bone resorption, improve bone healing in animal and human studies, and reduce the prevalence of some fragility fractures in postmenopausal women. In the August 19, 2020 issue of The Journal, Bhandari et al. present the results of a randomized trial comparing romosozumab to placebo in the healing of tibial diaphyseal fractures treated with intramedullary (IM) nails. Tibial shaft fractures are common in adults, but even after IM nail fixation there is a significant rate of healing failure and subpar functional outcomes with this fracture type.
The study by Bhandari et al. was very well designed and conducted with high-quality data collection. In terms of the primary outcome—median time to radiographic healing—there was no significant difference between the placebo group (n=100) and 9 romosozumab groups (n=293 total, testing 3 different dose levels and 3 different frequencies). Additionally, analysis revealed no differences between placebo and romosozumab groups in median time to clinical healing or in changes in physical function from baseline. (See related OrthoBuzz post about a recent randomized trial investigating romosozumab for hip fractures.)
Kudos to Amgen for funding the trial and for allowing the 66-center, international academic consortium that conducted it to publish the results, warts and all. Such negative findings appropriately inform decisions about which compounds to investigate and about study designs for retesting the same compounds. For example, Bhandari et al. encourage further study of romosozumab in tibial-fracture patients at high risk of poor fracture healing, such as those with diabetes or patients undergoing treatment with corticosteroids.
We are likely to see many such “failures” in the search for pharmacological adjuncts to improve fracture healing, but it seems our orthopaedic community has laid out a clear roadmap for studying this important question further.
Marc Swiontkowski, MD
OrthoBuzz regularly brings you a current commentary on a “classic” article from The Journal of Bone & Joint Surgery. These articles have been selected by the Editor-in-Chief and Deputy Editors of The Journal because of their long-standing significance to the orthopaedic community and the many citations they receive in the literature. Our OrthoBuzz commentators highlight the impact that these JBJS articles have had on the practice of orthopaedics. Please feel free to join the conversation about these classics by clicking on the “Leave a Comment” button in the box to the left.
Prior to the innovative work of Gus Sarmiento in the 1960s, most orthopaedic surgeons treated tibial shaft fractures with a prolonged period of immobilization, in a long-leg non-weight bearing cast. While the fracture usually healed, knee joint stiffness and atrophy of the entire limb usually resulted as well.
In this 1967 JBJS classic, Sarmiento extended the concept of early weight-bearing treatment of these fracture as advocated by Dehne and others by incorporating the limb in a below-the-knee total-contact plaster cast, a technique that had recently been developed for the early rehabilitation of a below-the-knee amputation. The skin-tight plaster cast was applied over a single layer of stockinette one to two weeks after the acute swelling had subsided. It was molded proximally to contain the muscles of the proximal leg, and it had medial and lateral condylar flares, similar to a patellar-tendon-bearing (PTB) prosthesis.
Sarmiento encouraged early weight bearing in the cast, as he believed that doing so stimulated fracture healing. His confidence was borne out by this report of 100 consecutive tibial shaft fractures treated with a PTB cast. All 100 fractures healed, and healing occurred with minimal deformity or shortening. This success soon led to Sarmiento’s development of a functional below-the-knee tibial fracture brace made of Orthoplast®, a thermoplastic material which, when heated in a water bath, could be molded easily to the injured limb.
While today most tibial shaft fractures are treated with intramedullary nails, the principles developed by Sarmiento still apply, as the nail acts much like the fracture brace to maintain alignment during the healing process. Fracture healing is enhanced by weight bearing, and joint stiffness and muscle atrophy are avoided by early motion.
Sarmiento’s concept of functional treatment was later extended to the treatment of humeral and ulnar shaft fractures, which commonly continue today to be managed effectively with fracture braces that he developed. This emphasis upon early functional restoration while the fracture is healing has allowed many patients to achieve faster healing and to resume full function much sooner.
James D. Heckman, MD
JBJS Editor Emeritus