Differences in bone quality in low- and high-turnover renal osteodystrophy.

Abnormal bone turnover is common in CKD, but its effects on bone quality remain unclear. We qualitatively screened iliac crest bone specimens from patients on dialysis to identify those patients with low (n=18) or high (n=17) bone turnover. In addition, we obtained control bone specimens from 12 healthy volunteers with normal kidney function. In the patient and control specimens, Fourier transform infrared spectroscopy and nanoindentation quantified the material and mechanical properties of the specimens, and we used bone histomorphometry to assess parameters of bone microstructure and bone formation and resorption. Compared with high or normal turnover, bone with low turnover had microstructural abnormalities such as lower cancellous bone volume and reduced trabecular thickness. Compared with normal or low turnover, bone with high turnover had material and nanomechanical abnormalities such as reduced mineral to matrix ratio and lower stiffness. These data suggest that turnover-related alterations in bone quality may contribute to the diminished mechanical competence of bone in CKD, albeit through different mechanisms. Therapies tailored specifically to low- or high-turnover bone may treat renal osteodystrophy more effectively.

Evaluating bone quality in patients with chronic kidney disease.

Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease-mineral and bone disorder (CKD-MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD-MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD-MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD-MBD should aid in the development of new modalities to prevent, or treat, these abnormalities.

Low-energy fractures without low T-scores characteristic of osteoporosis: a possible bone matrix disorder.

BACKGROUND: Osteoporotic fractures commonly occur after low-energy trauma in postmenopausal women with reduced bone quantity documented by low bone mineral density (BMD). Low-energy fractures, however, have also been reported to occur in premenopausal women with normal or near-normal BMD, suggesting the existence of a bone quality abnormality. METHODS: Bone quality and quantity were evaluated in a cross-sectional study of three groups of premenopausal white females: (1) twenty-five subjects with low-energy fracture(s) and BMD in the normal range (t-scores > -2.0), (2) eighteen subjects with low-energy fracture(s) and BMD in the osteoporotic range (t-scores ≤ -2.5), and (3) fourteen healthy volunteers (controls). Bone quality was assessed with use of Fourier transform infrared spectroscopy and histomorphometry in iliac crest bone samples obtained from all subjects; bone quantity was assessed by dual x-ray absorptiometry and histomorphometry. RESULTS: The collagen crosslinking ratio in the non-low-BMD subjects with fractures was 13% greater than the ratio in the low-BMD subjects with fractures and 14% greater than the ratio in the controls (p < 0.001 for both). Cancellous bone volume was 29% greater (p < 0.01) and trabecular separation was 31% less (p < 0.01) in the non-low-BMD subjects with fractures than in the low-BMD subjects with fractures; the values in the non-low-BMD subjects did not differ from those in the controls. Bone turnover did not differ among the groups, and osteomalacia was not present in any subject. Thus, the non-low-BMD subjects with fractures maintained bone quantity, but the collagen crosslinking ratio, a parameter of bone quality, was abnormal. In contrast, the low-BMD subjects with fractures did not have this collagen crosslinking abnormality but did have abnormal bone quantity. CONCLUSIONS: This study highlights a collagen crosslinking abnormality in patients with low-energy fractures and nonosteoporotic t-scores. Reports have indicated that altered collagen crosslinking is associated with subnormal fracture resistance. A finding of nonosteoporotic bone mass in a patient with low-energy fractures would justify assessment of bone material quality, which currently requires a bone biopsy. Further studies are needed to search for possible noninvasive tests to diagnose abnormal crosslinking. Since no specific therapies for abnormal collagen crosslinking are currently available, studies are also needed to explore novel therapeutic modalities to reverse the underlying collagen crosslinking abnormality. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.