Site-Dependent Reference Point Microindentation Complements Clinical Measures for Improved Fracture Risk Assessment at the Human Femoral Neck

Abstract

In contrast to traditional approaches to fracture risk assessment using clinical risk factors and bone mineral density (BMD), a new technique, reference point microindentation (RPI), permits direct assessment of bone quality; in vivo tibial RPI measurements appear to discriminate patients with a fragility fracture from controls. However, it is unclear how this relates to the site of the most clinically devastating fracture, the femoral neck, and whether RPI provides information complementary to that from existing assessments. Femoral neck samples were collected at surgery after low-trauma hip fracture (n ¼ 46; 17 male; aged 83 [interquartile range 77-87] years) and compared, using RPI (Biodent Hfc), with 16 cadaveric control samples, free from bone disease (7 male; aged 65 years). A subset of fracture patients returned for dual-energy X-ray absorptiometry (DXA) assessment (Hologic Discovery) and, for the controls, a micro-computed tomography setup (HMX, Nikon) was used to replicate DXA scans. The indentation depth was greater in femoral neck samples from osteoporotic fracture patients than controls (p < 0.001), which persisted with adjustment for age, sex, body mass index (BMI), and height (p < 0.001) but was site-dependent, being less pronounced in the inferomedial region. RPI demonstrated good discrimination between fracture and controls using receiver-operating characteristic (ROC) analyses (area under the curve [AUC] ¼ 0.79 to 0.89), and a model combining RPI to clinical risk factors or BMD performed better than the individual components (AUC ¼ 0.88 to 0.99). In conclusion, RPI at the femoral neck discriminated fracture cases from controls independent of BMD and traditional risk factors but dependent on location. The clinical RPI device may, therefore, supplement risk assessment and requires testing in prospective cohorts and comparison between the clinically accessible tibia and the femoral neck.

Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease

“…Other report revealed that cortical porosity is not superior to BMD determined by DXA hofr identification of HD patients with fragility fracture [133]. Moreover, clinical assessment of human femoral mechanical properties by reference point indentation (RPI), which is a novel technique that allows direct measurement of bone material or biomechanical properties, indicated that BMD did not discriminate fracture cases form controls [134]. These recent studies suggest that bone strength in CKD patients may be affected by many factors in a complicated manner, and the major factor and its degree of contribution remain unidentified.…”

Tissue-Level Mechanical Properties of Bone Contributing to Fracture Risk

“…Jenkins et al[66] undertook cRPI measurements (10 cycles up to 10 N) on femoral neck samples collected at surgery after low-trauma hip fracture (interquartile range 77–87 yo, n=46 with 17 males) and from cadaveric controls (interquartile range 61–74 yo, n=16 with 7 males). Again, bone from osteoporotic fracture patients was less resistant to microindentation than bone from controls, even after adjusting for cofounding factors (age, sex, BMI, and height).…”

Clinical experience with microindentation in vivo in humans

“…Preclinical results also support the effectiveness of treatments on RPI properties, independently of BMD changes [47]. [48] for cyclic microindentation, but must also be studied for the impact microindentation tests appropriate for clinical use.…”