The quality of bone in the skeleton depends on the amount of bone, geometry, microarchitecture and material properties, and the molecular and cellular regulation of bone turnover and repair. This study aimed to identify material and structural factors that alter in fragility hip fracture patients treated with antiresorption therapies (FxAr) compared to fragility hip fracture patients not on treatment (Fx).

Bone from the intertrochanteric site, femoral head (FH: FxAr = 5, Fx = 8), compression screw cores and box chisel were obtained from patients undergoing hemi-arthroplasty surgery, FxAr (6f, 2m, mean 79 and range [64–89] years), and Fx (7f, 1m, age 85 [75–93] years). Control bone was obtained at autopsy (9f, 4m, 77 [65–88] years). Treated patients were on various bisphosphonates. Samples were resin-embedded, for quantitative backscattered electron imaging of the degree of mineralisation and assessment of bone architecture. Trabecular bone volume fraction (BV/TV) and architectural parameters were not significantly different between FxAr and Fx groups.

Both groups showed normal distributions of weight (wt) % Ca; however, the FxAr was less mineralised than the Fx and the control group (mean wt % Ca: FxAr = 24.3%, Fx = 24.8%, Control = 24.9%). When comparing the FH specimens only, we found that BV/TV in the FxAr was greater than the Fx group (18% vs 15%). All other parameters were not significantly different. In addition, the mineralisation was greater in the FxAr group compared to the Fx group (25.5 % vs 25.0%) but was not significantly different.

Collectively, these data suggest the effect on bone of antiresorptives may be different for patients on antiresorptive treatment that do not subsequently fracture. Assessment of bone material property data together with other bone quality measures may hold the key to better understanding of antiresorptive treatment efficacy.

Evidence is accumulating for the role of bone in the pathogenesis of osteoarthritis (OA). Previous studies have shown a generalised increase in bone mass and hypo-mineralisation in OA patients. However, the molecular and cellular mechanisms involved in the increased bone mass and matrix compositional profiles in OA, at distal skeletal sites to the articular cartilage, have not yet been well defined. This study examined whether gene expression of bone anabolic factors, trabecular bone architecture and matrix mineralisation are altered in human OA and non-OA hipbone. Intertrochanteric (IT) trabecular bone samples were obtained from 15 primary hip OA patients (mean age 65 [48–85] years) and 13 closely age- and gender-matched autopsy controls (mean age 63 [44–83] years). Semi-quantitative RT-PCR analysis revealed elevated mRNA expression levels of alkaline phosphatase (p < 0.002), osteocalcin (p < 0.0001), osteopontin (p < 0.05), collagen type-I α chains COL1A1 (p < 0.0001) and COL1A2 (p < 0.002), in OA bone compared to control, suggesting possible increases in osteoblastic biosynthetic activity and/or bone turnover at the IT region in OA. Interestingly, the ratio of COL1A1:COL1A2 mRNA was almost 2-fold greater in OA bone compared to control (p < 0.001), suggesting the potential presence of collagen type-I homotrimer at the distal site that may associate with hypomineralisation in OA individuals. Using a quantitative backscatter electron imaging technique, mineralisation profiles of IT trabecular bone indicated decreased mineralisation in the OA group compared to the control group (24.2 weight percent calcium [wt%Ca] versus 25.3 wt%Ca). Bone histomorphometric analysis found OA IT bone had increased surface density of bone and decreased trabecular separation compared to control bone. Taken together with a reported increase in diffuse microdamage in OA IT bone (Fazzalari et al. Bone 31:697–702, 2002), possibly due to hypomineralisation, these results are consistent with the altered bone material properties found in OA individuals. The finding of differential gene expression, altered mineralisation and architectural changes in OA bone, at a skeletal site distal to the active site of joint degeneration, supports the concept of systemic involvement of bone in the pathogenesis of OA.

The presence of microdamage in bone and its targeted repair by activating bone remodelling has been controversial partly because it is difficult to locate and difficult to quantify. A number of studies have now validated techniques to locate and quantify microdamage and microdamage repair in human cortical and trabecular bone samples. The purpose of this study is to determine if microcracks accumulate in the cancellous bone of the intertrochanteric region of the proximal femoral shaft and influence the strength of bone. We have used en bloc basic fuchsin staining to identify in vivo microcracks in 70 micron sections. Trabecular bone was sampled in 33 patients undergoing total hip replacement for primary osteoarthritis. The study sample had a median age of 73 years and included 18 women (aged 49 to 84 years) and 15 men (aged 45 to 85 years). Histomorphometry was used to quantify the number of cracks in each case. In a selection of 12 cases the bone sample was also biomechanically tested to determine the cancellous bone strength. We found that microcracks accumulate with age, particularly after the age of about 60 years. This indicates that the bone from the elderly is more susceptible to fatigue damage than bone from the young. In addition, an increased number of microcracks in the cancellous bone significantly reduced the ultimate failure stress of the bone. Bone screws or pins placed in cortical or trabecular bone create microdamage adjacent to an implant, and the area in which this microdamage occurs is the same as that which subsequently remodels. Microdamage may be the result primarily of procedures during prosthetic implantation, but bone screws or pins can create stress concentrations that can be sites for initiation of new cracks. Therefore, if bone remodelling targets bone microdamage for repair then accumulation of microdamage around prosthetic implants may be responsible for the biologic responses which lead to implant loosening. This phenomenon is understudied in orthopaedic research and is an area requiring further investigation.

The cellular and molecular mechanisms that lead to particular trabecular structures in healthy bone and in skeletal disease, such as osteoarthritis (OA), are poorly understood. Osteoclast differentiation factor (ODF) is a newly described regulator of osteoclast formation and function, whose activity appears to be a balance between interaction with its receptor, RANK, and with an antagonist binding protein, osteoprotegerin (OPG). We have examined the relationship between the expression of ODF, RANK and OPG mRNA, and parameters of bone structure and turnover, in human trabecular bone. Intertrochanteric trabecular bone was sampled from patients with primary hip OA (n=13; median age 66 years) and controls taken at autopsy (n=12; median age 68.5 years), processed for histomorphometric analysis and RNA isolated for RT-PCR analysis of ODF, RANK and OPG mRNA expression. The ratios of ODF/OPG and ODF/RANK mRNA are significantly lower in OA (1.78±0.98; 0.59±0.31) compared to the controls (3.41±1.94, p< 0.02; 2.53±1.5, p< 0.001). This suggests that in OA there is less ODF mRNA available per unit RANK mRNA, and that osteoclast formation may be reduced. Furthermore, eroded bone surface (ES/BS[%]) was significantly lower (p< 0.05) in the OA group (6.37±3.17) compared to controls (9.74±4.53). Stong associations were found between the ratio of ODF/OPG mRNA and bone volume (ODF/OPG vs BV/TV[%], r=−0.67; p0.05) and bone turnover (ODF/OPG vs ES/BS, r=0.93; p< 0.001; ODF/OPG vs osteoid surgace (OS/BS[%], r=0.80; p< 0.001) in controls. In contrast to controls, these relationships were not evident in the OA group, suggesting that bone turnover maybe regulated differently in this disease.