The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student Objectives
Methods
We report the outcome of 84 nonunions involving
long bones which were treated with rhBMP-7, in 84 patients (60 men:
24 women) with a mean age 46 years (18 to 81) between 2003 and 2011.
The patients had undergone a mean of three previous operations (one
to 11) for nonunion which had been present for a mean of 17 months
(4 months to 20 years). The nonunions involved the lower limb in
71 patients and the remainder involved the upper limb. A total of 30
nonunions were septic. Treatment was considered successful when
the nonunion healed without additional procedures. The relationship
between successful union and the time to union was investigated
and various factors including age and gender, the nature of the
nonunion (location, size, type, chronicity, previous procedures,
infection, the condition of the soft tissues) and type of index
procedure (revision of fixation, type of graft, amount of rhBMP-7) were
analysed. The improvement of the patients’ quality of life was estimated
using the Short Form (SF) 12 score. A total of 68 nonunions (80.9%) healed with no need for further
procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate
logistic regression analysis of the factors affecting union suggested
that only infection significantly affected the rate of union
(p = 0.004).Time to union was only affected by the number of previous
failed procedures
(p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and
mental score, respectively, was noted within the first post-operative
year. Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion
and improved quality of life in about 80% of patients. Aseptic nonunions
were much more likely to unite than septic ones. The number of previous
failed operations significantly delayed the time to union. Cite this article:
Heterotopic ossification occurring after the use of commercially available bone morphogenetic proteins has not been widely reported. We describe four cases of heterotopic ossification in patients treated with either recombinant bone morphogenetic protein 2 or recombinant
