Bone material properties in premenopausal women with idiopathic osteoporosis

Abstract

Idiopathic osteoporosis (IOP) in premenopausal women is characterized by fragility fractures at low or normal bone mineral density (BMD) in otherwise healthy women with normal gonadal function. Histomorphometric analysis of transiliac bone biopsy samples has revealed microarchitectural deterioration of cancellous bone and thinner cortices. To examine bone material quality, we measured the bone mineralization density distribution (BMDD) in biopsy samples by quantitative backscattered electron imaging (qBEI), and mineral/matrix ratio, mineral crystallinity/maturity, relative proteoglycan content and collagen cross-link ratio at actively bone forming trabecular surfaces by Raman and Fourier Transform Infrared (FTIRM) microspectroscopic techniques. The study groups included: premenopausal women with idiopathic fractures (IOP, n=45), or idiopathic low BMD (Z-score ≤-2.0 at spine and/or hip) but no fractures (ILBMD, n=19), and healthy controls (CONTROL, n=38). BMDD of cancellous bone showed slightly lower mineral content in IOP (both Cn.CaMean and Cn.CaPeak are 1.4% lower) and in ILBMD (both are 1.6% lower, p<0.05) versus CONTROL, but no difference between IOP and ILBMD. Similar differences were found when affected groups were combined versus CONTROL. The differences remained significant after adjustment for mineralizing surface (MS/BS), suggesting that the reduced mineralization of bone matrix cannot be completely accounted for by differences in bone turnover. Raman and FTIRM analysis at forming bone surfaces showed no differences between combined IOP/ILBMD groups versus CONTROL, with the exceptions of increased proteoglycan content per mineral content and increased collagen cross-link ratio. When the two affected subgroups were considered individually, mineral/matrix ratio and collagen cross-link ratio were higher in IOP than ILBMD. In conclusion, our findings suggest that bone material properties differ between premenopausal women with IOP/ILBMD and normal controls. In particular, the altered collagen properties at sites of active bone formation support the hypothesis that affected women have osteoblast dysfunction that may play a role in bone fragility.

Bone composition: relationship to bone fragility and antiosteoporotic drug effects

“…16 Parameters obtained from BMDD include the average and mode Ca content and the full-width at half-maximum of the BMDD peak, which is a measure of the heterogeneity of mineralization. Deviations from normal calcium distributions have been reported to date in: osteomalacia, 17 osteoporosis 18 and idiopathic osteoporosis 19 (peak shifted to the left of normal), classical and new forms of osteogenesis imperfecta 16,20 (peak shifted to the right of normal) and treatment with some but not all bisphosphonates examined by this technique. 18,21,22 Variation in phosphate distribution is visualized by both Fourier transform infrared microscopic imaging (FTIRI) 23 and Raman microscopy and imaging (Raman).…”

Aging Versus Postmenopausal Osteoporosis: Bone Composition and Maturation Kinetics at Actively-Forming Trabecular Surfaces of Female Subjects Aged 1 to 84 Years

“…(53)(54)(55) Interestingly, in cases where predicted bone strength and actual fracture incidence considerations were divergent, collagen enzymatic cross-links, to date, always correlated with the latter. (18,48,50,52,(56)(57)(58)(59) One possible explanation for this is that although stiffness depends on modulus, bone toughness depends on interfaces, (60) and in the actively-forming trabecular bone areas examined in the present study a major interface close to TA3 is present, namely the cement line. (61) This hypothesis is further supported by results obtained in antler bone, which infer that extrinsic/microscale collagen-based characteristics and hypermineralized seams/ "zones" may play an important role in imparting the remarkable bone toughness seen in antler.…”

The effect of rheumatoid arthritis and functional loading on the structure of the mandibular condyle in a transgenic mouse model: An FTIR study

“…In a similar study, a comparison of trauma specimens from osteoporotic femoral bone fractures in women with control subjects has not revealed any differences in the mineral-to-matrix ratios as well (p=0.11). 28 Analogous research in tissue specimens of long bones from osteoporosis 29 or experimental arthritis and osteogenesis imperfecta models/patients, using FTIR or Raman spectroscopy are in agreement regarding the non-compromised mineral bone phase in the diseased state. 30,31 It has been suggested that matrix proteoglycans are capable of regulating hydroxyapatite formation and nucleation; 32 apparently, the minimal amounts of PG destruction in all groups as identified in the overlying condylar cartilage in the present study may denote a similar condition taking place in the closely related subcartilage bone.…”