Biopsies from patients with sacral insufficiency fracture are characterized by low bone matrix mineralization and high turnover

Abstract

Sacral insufficiency fractures are known to occur primarily in older women without adequate trauma. While an association with low bone mineral density (i.e., osteoporosis) has been reported, more detailed information on local bone quality properties in affected patients is not available. In the present study, core biopsies were obtained from the S1 sacral ala in patients with a bilateral sacral insufficiency fracture (type IV according to the fragility fractures of the pelvis (FFP) classification) who required surgical stabilization. Dual energy X-ray absorptiometry (DXA) and laboratory bone metabolism analyses were performed. For comparison, control biopsies were acquired from skeletally intact age- and sex-matched donors during autopsy. A total of 31 biopsies (fracture: n = 19; control: n = 12) were evaluated by micro-computed tomography (μ-CT), histomorphometry on undecalcified sections, and quantitative backscattered electron imaging (qBEI). DXA measurements showed mean T-scores in the range of osteoporosis in the fracture cohort (T-scoremin -2.6 ± 0.8). Biochemical analysis of bone metabolism parameters revealed high serum alkaline phosphatase and urinary deoxypyridinoline/creatinine levels. In the biopsies, a loss of trabecular microstructure along with increased osteoid values were detected in the fracture patients compared to controls (osteoid volume per bone volume 5.9 ± 3.5 vs. 0.9 ± 0.5%, p < 0.001). We also found evidence of microfractures with chronic healing processes (i.e., microcallus) as well as pronounced hypomineralization in the biopsies of the fracture cohort compared to the controls as evidenced by lower CaMean measured by qBEI (22.5 ± 1.6 vs. 24.2 ± 0.5 wt%, p = 0.003). In conclusion, this high-resolution biopsy study provides evidence of local hypomineralization in patients with sacral insufficiency fractures, pointing to reduced fracture resistance but also a distinct phenotype other than the predominant loss of trabeculae as in postmenopausal osteoporosis. Our data highlight the importance of therapies that promote bone mineralization to optimally treat and prevent sacral insufficiency fractures.