Time course changes to structural, mechanical and material properties of bone in rats after complete spinal cord injury.

OBJECTIVE: Characterise the spatiotemporal trabecular and cortical bone responses to complete spinal cord injury (SCI) in young rats. METHODS: 8-week-old male Wistar rats received T9-transection SCI and were euthanised 2-, 6-, 10- or 16-weeks post-surgery. Outcome measures were assessed using micro-computed tomography, mechanical testing, serum markers and Fourier-transform infrared spectroscopy. RESULTS: The trabecular and cortical bone responses to SCI are site-specific. Metaphyseal trabecular BV/TV was 59% lower, characterised by fewer and thinner trabeculae at 2-weeks post-SCI, while epiphyseal BV/TV was 23% lower with maintained connectivity. At later-time points, metaphyseal BV/TV remained unchanged, while epiphyseal BV/TV increased. The total area of metaphyseal and mid-diaphyseal cortical bone were lower from 2-weeks and between 6- and 10-weeks post-SCI, respectively. This suggested that SCI-induced bone changes observed in the rat model were not solely attributable to bone loss, but also to suppressed bone growth. No tissue mineral density differences were observed at any time-point, suggesting that decreased whole-bone mechanical properties were primarily the result of changes to the spatial distribution of bone. CONCLUSION: Young SCI rat trabecular bone changes resemble those observed clinically in adult and paediatric SCI, while cortical bone changes resemble paediatric SCI only.

Generalized Uncoupled Bone Remodeling Associated With Delayed Healing of Fatigue Fractures.

Fatigue fractures in bones are common injuries with load-bearing activities, during which the remodeling aimed at removing microdamage has been suggested to play a role in increasing related fracture risk. Much attention has been given to the uncoupling between osteoclastic bone resorption and osteoblastic osteogenesis in fatigue fracture cases; however, the underlying pathophysiologic mechanisms of impaired fracture healing are yet unknown. Here we report multiple fatigue fractures in a physically active woman receiving contraceptive pills for years. Her fracture healing was remarkably slow, although she has been otherwise healthy. The patient underwent bone biopsy of the iliac crest that showed remarkable peritrabecular fibrosis with increased osteoclastic bone resorption combined with relatively low bone formation. Analysis of bone biochemical composition revealed a more complex picture: First, notable declines in bone mineral content-based parameters indicating abnormal mineralization were evident in both cancellous and cortical bone. Second, there was elevation in mineral crystal size, perfection, and collagen maturity in her bone tissues from different anatomical sites. To our knowledge, this is the first report showing generalized uncoupling in bone remodeling, increased peritrabecular fibrosis, and bone compositional changes associated with delayed healing of fatigue fractures. These results may explain delayed healing of fatigue and stress fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Increased heterogeneity of bone matrix mineralization in pediatric patients prone to fractures: a biopsy study.

Idiopathic osteoporosis (IOP) in children is characterized by fragility fractures and/or low bone mineral density in otherwise healthy individuals. The aim of the present work was to measure bone mineralization density distribution (BMDD) based on quantitative backscattered electron imaging (qBEI) in children with suspected IOP. Entire cross-sectional areas of transiliac bone biopsy samples from children (n = 24, 17 boys; aged 6.7-16.6 years) with a history of fractures (n = 14 with at least one vertebral fracture) were analyzed for cancellous (Cn) and cortical (Ct) BMDD. Outcomes were compared with normal reference BMDD data and correlated with the patients' clinical characteristics and bone histomorphometry findings. The subjects had similar average degree but significantly higher heterogeneity of mineralization in both Cn and Ct bone (Cn.CaWidth +23%, Ct.CaWidth +15%, p < 0.001 and p = 0.002, respectively), together with higher percentages of low mineralized cancellous (Cn.CaLow +35%, p < 0.001) and highly mineralized cortical bone areas (Ct.CaHigh +82%, p = 0.032). Ct.CaWidth and Ct.CaLow were positively correlated with mineralizing surface per bone surface (MS/BS; a primary histomorphometric determinant of bone formation) and with serum bone turnover markers (all p < 0.05). The correlations of the mineralization heterogeneity with histomorphometric and serum bone turnover indices suggest that an enhanced variation in bone turnover/formation contributes to the increased heterogeneity of mineralization. However, it remains unclear whether the latter is cause for, or the response to the increased bone fragility in these children with suspected IOP.

Incidence and bone biopsy findings of atypical femoral fractures.

Bisphosphonates are widely used in the treatment of osteoporosis. It has been suggested that bisphosphonate treatment may be associated with atypical femoral fractures (AFFs), severely suppressed bone turnover rate, and decreased mineralization. We studied bone properties using bone quantitative histomorphometry and Fourier transform infrared spectroscopic imaging (FTIRI) on patients with AFFs. Further, the incidence of AFFs was estimated. Patient records of Kuopio University Hospital, Finland from January 2007 to June 2009 were reviewed to identify all patients who had sustained and had been operated for AFF (n = 8). The incidence of AFFs among patients on bisphosphonates was 0.61 fractures/1,000 patients per year, compared to 0.0067/1,000 per year among untreated patients. The patients that underwent bone biopsy (n = 4) were postmenopausal women (aged 55.5-81.1 years) who had been treated with bisphosphonates for over 4 years. Histomorphometry revealed low trabecular bone volume. Bone formation and resorption parameters tended to be low. Trabecular bone single labels were detected in one patient in the region of interest. In the extended label search, trabecular bone double labels were found in two patients. Based on FTIRI results, higher phosphate-to-amide I ratio and collagen maturity were found compared to normal samples. The heterogeneity of phosphate-to-amide I ratio was low. Overall incidence of atypical femoral fractures is low. The poor fracture resistance in some patients on long-term bisphosphonate-therapy could be explained by low bone formation, and changes in bone composition, i.e., higher degree of mineralization, increased collagen maturity, and decreased heterogeneity of the degree of mineralization.

Altered bone composition in children with vertebral fracture.

Primary osteoporosis in children often leads to vertebral fractures, but it remains unknown whether these fractures associate with changes in bone composition. This study aimed to determine the differences in bone composition in fracture-prone children with and without vertebral fractures, as assessed by Fourier transform infrared spectroscopic imaging (FTIRI) and bone histomorphometry. Iliac crest bone biopsies (n = 24) were obtained from children who were suspected of primary osteoporosis based on evidence from the fracture history and/or low bone mineral density (BMD) by dual-energy X-ray absorptiometry. Vertebral morphology was determined by radiography. Bone biopsies were analyzed using histomorphometry and FTIRI. Phosphate-to-amide I, carbonate-to-phosphate, carbonate-to-amide I, and cross-link ratio (collagen maturity) were calculated. Children with (n = 14) and without (n = 10) vertebral fracture were compared. Low cancellous bone volume (BV/TV) was detected by histomorphometry in 36% of the children with vertebral fracture, and bone turnover rate was abnormal in 64% of them. Children with vertebral fractures had lower carbonate-to-phosphate ratios (p < .05) and higher collagen maturity (p < .05) than children without vertebral fracture. The children with low BV/TV in biopsy showed lower carbonate-to-amide I ratios (p < .05) than the children with normal bone volume. This study showed changes in bone composition among fracture-prone children who had sustained a vertebral fracture. The observed changes in bone composition in these children may contribute to their greater propensity to sustain vertebral fractures.

Infrared spectroscopy indicates altered bone turnover and remodeling activity in renal osteodystrophy.

Renal osteodystrophy alters metabolic activity and remodeling rate of bone and also may lead to different bone composition. The objective of this study was to characterize the composition of bone in high-turnover renal osteodystrophy patients by means of Fourier transform infrared spectroscopic imaging (FTIRI). Iliac crest biopsies from healthy bone (n = 11) and patients with renal osteodystrophy (ROD, n = 11) were used in this study. The ROD samples were from patients with hyperparathyroid disease. By using FTIRI, phosphate-to-amide I ratio (mineral-to-matrix ratio), carbonate-to-phosphate ratio, and carbonate-to-amide I ratio (turnover rate/remodeling activity), as well as the collagen cross-link ratio (collagen maturity), were quantified. Histomorphometric analyses were conducted for comparison. The ROD samples showed significantly lower carbonate-to-phosphate (p < .01) and carbonate-to-amide I (p < .001) ratios. The spatial variation across the trabeculae highlighted a significantly lower degree of mineralization (p < .05) at the edges of the trabeculae in the ROD samples than in normal bone. Statistically significant linear correlations were found between histomorphometric parameters related to bone-remodeling activity and number of bone cells and FTIRI-calculated parameters based on carbonate-to-phosphate and carbonate-to-amide I ratios. Hence the results suggested that FTIRI parameters related to carbonate may be indicative of turnover and remodeling rate of bone.