Impaired organic and mineral extracellular matrix composition in early-onset osteoporosis.

Early-onset osteoporosis (EOOP) is a rare form of primary osteoporosis defined by major skeletal fractures or low BMD that occurs in early age. However, the characteristics of the extracellular matrix that may contribute to bone fragility are unknown. We explored the microarchitecture and bone matrix composition in transiliac bone biopsies (BBs) obtained from adults with EOOP. We compared EOOP BBs to historical control BBs. Microarchitecture was measured by μCT and bone matrix composition by Raman microspectroscopy and Fourier transform infrared spectroscopy. Mechanical response of the bone matrix was investigated by nanoindentation. The contribution of each parameter was assessed by principal component analysis. We compared 18 BBs for EOOP patients (mean [SD] age 34 [8] yr, LS BMD Z-score -2.05 [1.04]) to 19 BBs for age-matched healthy individuals. Patients had vertebral fractures only (n = 7), peripheral fracture only (n = 6) and both vertebral and peripheral fractures (n = 3). Early-onset osteoporosis and controls had similar bone volume (bone volume/total volume, p = .741). As compared with controls, EOOP BBs showed lower trabecular separation (p = .026) and higher trabecular connectivity density (p < .001); cortical thickness was lower in EOOP BBs (p < .01). Also, GAG/Amide III and hydroxyproline/proline ratios as well as accumulation of AGEs were greater in EOOP than controls (all p < .0001). Moreover, tissue mineralization was lower in EOOP than controls, as shown by v1PO4/CH2 ratio, mineral maturity crystallinity and crystal size index (all p < .005). Hardness, indentation modulus and maximum load were all altered in EOOP. Principal component analysis revealed greater contribution of both the organic and mineral matrix phase at the trabecular and cortical EOOP bone rather than bone microarchitecture. The matrix composition of bone showed greater damage of the organic matrix phase and reduced mineralization in EOOP patients than controls, which may explain the high risk of fracture in EOOP patients and may differentiate EOOP from other bone diseases.