Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures.

Orthopaedics, Linköping University, Linköping, Sweden.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research (Impact Factor: 6.04). 08/2009; 25(2):404-14. DOI: 10.1359/jbmr.090731
Source: PubMed

ABSTRACT Animal experiments show a dramatic improvement in skeletal repair by teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20 microg dose normally used for osteoporosis treatment or higher, would accelerate fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were randomly assigned to 8 weeks of once-daily injections of placebo (n = 34) or teriparatide 20 microg (n = 34) or teriparatide 40 microg (n = 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning with the teriparatide 40 microg versus placebo comparison, using a gatekeeping strategy. The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8 weeks for placebo and teriparatide 20 microg and 40 microg, respectively (overall p = .015). There was no significant difference between the teriparatide 40 microg versus placebo groups (p = .523). In post hoc analyses, there was no significant difference between teriparatide 40 microg versus 20 microg (p = .053); however, the time to healing was shorter in teriparatide 20 microg than placebo (p = .006). The primary hypothesis that teriparatide 40 microg would shorten the time to cortical bridging was not supported. The shortened time to healing for teriparatide 20 microg compared with placebo still may suggest that fracture repair can be accelerated by teriparatide, but this result should be interpreted with caution and warrants further study.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bone fracture healing impairment related to mechanical problems has been largely corrected by advances in fracture management. Better protocols, more strict controls of time and function, hardware and surgical technique evolution have contributed to better prognosis, even in complex fractures. However, atrophic nonunion persists in clinical cases where, for different reasons, the osteogenic capability is impaired. When this is the case, a better understanding of basic mechanisms under bone repair and augmentation techniques may put in perspective the current possibilities and future opportunities. Among those, cell therapy particularly aims to correct this insufficient osteogenesis. However, the launching of safe and efficacious cell therapies still requires substantial amount of research, especially clinical trials. This review will envisage the current clinical trials on bone healing augmentation based on cell therapy, with the experience provided by the REBORNE Project, and the insight from investigator-driven clinical trials on advanced therapies towards the future.
    Bone 08/2014; · 4.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antioxidants were implicated as potential reagents to enhance osteogenesis, and nano-fullerenes have been demonstrated to have a great antioxidative capacity by both in vitro and in vivo experiments. In this study, we assessed the impact of a polyhydroxylated fullerene, fullerol, on the osteogenic differentiation of human adipose-derived stem cells (ADSCs). Fullerol was not toxic against human ADSCs at concentrations up to 10 μM. At a concentration of 1 μM, fullerol reduced cellular reactive oxygen species after a 5-day incubation either in the presence or in the absence of osteogenic media. Pretreatment of fullerol for 7 days increased the osteogenic potential of human ADSCs. Furthermore, when incubated together with osteogenic medium, fullerol promoted osteogenic differentiation in a dose-dependent manner. Finally, fullerol proved to promote expression of FoxO1, a major functional isoform of forkhead box O transcription factors that defend against reactive oxygen species in bone. Although further clarification of related mechanisms is required, the findings may help further development of a novel approach for bone repair, using combined treatment of nano-fullerol with ADSCs.
    International Journal of Nanomedicine 01/2014; 9:4023-31. · 4.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fragility fractures are the most severe complications of osteoporosis and the poor mechanical properties of bone can make fixation and healing of these fracture extremely difficult. The role of orthopaedic surgeons does not end in skillful fixation of the fractures, but they have the unique opportunity to prevent complications which can negatively affect the patient's quality of life. The best practice for preventing the risk of further fractures in patients presenting fragility fractures includes fall prevention, investigation of possible causes underlying osteoporosis, attention to exercise, calcium and vitamin D supplementation as well as prescription of drugs. Actually two classes of agents can be used for their effect on fracture prevention: antiresorptive and bone forming agents. Systemic therapy reduces the risk of vertebral (30-70%) and non-vertebral fractures (12-53%), depending on agents and patients' compliance. Preclinical and clinical studies have shown that pharmacological agents involved in osteoporosis can also influence the phases of fracture repair. Preclinical studies and evidences from case reports showed a positive effect of anabolic drugs on bone healing and implant osseointegration. The interventions in the process of fracture healing had evolved from a diamond to a pentagon concept, with interactions between the mechanical environment, the local therapies, the vascularity of the fracture site, the biology of the host and the systemic therapy which has the potential to represent the fifth interaction factor. The orthopaedic surgeon plays a central role in clinical setting to evaluate the efficacy of systemic anti-fracture drugs for improving fracture repair and preventing complications.
    05/2014; 11(2):105-9.

Full-text (2 Sources)

Available from
Oct 2, 2014