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The amount of bone and the trabecular microarchitecture are two determinants of bone strength which can be quantified by bone histomorphometry. Among the parameters of bone microarchitecture, the Euler number developed in our laboratory (E( strut.cavity )) and trabecular bone pattern factor (TBPf) evaluate the connectivity and complexity independently of the bone quantity, and the speed of sound (SOS) measured by quantitative ultrasound (QUS) corroborates E( strut.cavity ). The aim of the present study was to validate E( strut.cavity ), TBPf, and SOS as parameters of bone microarchitecture and their contribution to bone strength. We examined 20 right os calcis taken after necropsy in 11 males and 9 females, aged 52-95 years. At the same anatomic location, we measured SOS and broadband ultrasound attenuation (BUA) using a Hologic Sahara device and bone mineral density (BMD) using a Hologic QDR 1000W. At this site a transcortical cylinder was cut for both apparent density measurement (Ap.Dens) and biomechanical tests (maximum compressive stress (sigma(max)) and Young's modulus (E)), and histomorphometry was performed with an automatic image analyzer (Visiolab, Explora Nova, France). E and sigma(max) were significantly correlated with the parameters of bone quantity, microarchitecture, and QUS. However, after adjustment for the bone quantity, E correlated only with E( strut.cavity ), TBPf, and SOS, and sigma(max) with BUA. In conclusion, the bone connectivity and complexity evaluated by E( strut.cavity ) and TBPf contribute to bone strength, independently of the bone quantity. The bone mechanical properties may be assessed, in os calcis, in the elastic domain by SOS and in the plastic domain by BUA.

In osteoporosis, bone fragility results from both bone loss and changes in trabecular microarchitecture, which can be quantified by bone histomorphometric parameters. Twenty human calcaneum were collected after necropsy. All measurements were performed at the same anatomical location. Bone histomorphometric parameters were measured on histological slides with an automatic image analyzer. The aims of our study were (1) to develop automatic measurements of four additional parameters reflecting trabecular network connectivity and complexity, i.e., trabecular bone pattern factor (TBPf), Euler number/tissue volume (Euler) according to the three definitions previously reported and to a fourth one established in the laboratory (Euler(strut.cavity)), marrow star volume, and interconnectivity index, and to determine their usefulness in microarchitecture characterization; and (2) to validate these parameters by evaluating their relationship with dual-energy X-ray absorptiometry and quantitative ultrasound (QUS) measurements performed on the same samples. The statistical analysis showed that TBPf and Euler(strut.cavity) appeared to be the most significant connectivity parameters, independently of bone quantity (bone mineral density, apparent density, cancellous bone volume). For QUS, after adjustment for bone quantity, only speed of sound (SOS) was significantly and negatively correlated to Euler(strut.cavity). Broadband ultrasound attenuation depends only on bone quantity. In conclusion, TBPf (a strut analysis parameter extrapolable in three dimensions) and Euler(strut.cavity) (the only bone connectivity parameter reflecting SOS) are two valid bone microarchitecture parameters. These new parameters were significantly correlated to the established trabecular structure parameters: trabecular thickness or trabecular spacing, being weakly correlated with SOS.

As previously reported, the age-related association between bone loss and increased marrow adipose volume may involve inhibitory effects of polyunsaturated fatty acids (PUFAs) potentially released by medullary adipocytes on osteoblastic proliferation and cell cycle progression. Because PUFAs have been reported to activate peroxisome proliferator-activated receptors (PPARs), we investigated the expression of these nuclear receptors in human primary osteoblastic (hOB) cells and examined the effects of natural PPAR ligands on hOB cell proliferation. We demonstrated basic expressions of PPARgamma and PPARbeta/delta in hOB cells at the protein level. As already shown for PUFAs, a short-term treatment with 15deoxy-Delta(12,14) -prostaglandin J2 (15dPGJ2) or prostacyclin (PGI2), which are specific ligands for PPARgamma and PPARbeta/delta, respectively, also significantly inhibited hOB cell proliferation. Given that the cell cycle withdrawal resulting from PPARgamma activation was often associated with the induction of cell differentiation, long-term effects of PUFAs and 15dPGJ2 were also assessed on the expression levels of transcription factors. PUFAs and 15dPGJ2 enhanced the expression of PPARgamma in hOB cells. It is of interest to note that PPARgamma protein level was dose-dependently increased, whereas that of Cbfal was decreased by a fatty acid-rich serum. In conclusion, this study shows that PPARgamma and beta/delta are expressed by hOB cells. The results further suggest that the short-term antiproliferative effect of PUFAs may involve PPAR activation in hOB cells, resulting in a cell cycle withdrawal favorable for the long-term differentiating effects of fatty acids. Further studies are now required to confirm the functional role of PPARs in the antiproliferative effects of PUFAs in hOB cells.

In order to evaluate the intersample variations for bone histomorphometric parameters in various metabolic bone diseases, either for a group or for one single patient, two complete contiguous transiliac bone biopsies were taken in 55 subjects. The diagnoses were osteoporosis (OP), renal osteodystrophy (ROD), osteomalacia (OM), primary hyperparathyroidism (HPT), metastatic bone disease, fluorosis, thyrotoxic bone, and "normal" bone. The following histomorphometric parameters were measured: trabecular bone volume (TBV), trabecular osteoid surfaces (TOS) and volume (TOV), trabecular resorption surfaces (TRS), and calcification rate (CR). The thickness index of osteoid seams (TIOS) was calculated. The measurements were performed with both manual and computerized methods which give similar results according to our previous study. The differences between parameters values measured on both cores were expressed by the difference in percent of the mean and by the intrapair coefficient of variation. Moreover, for each parameter, the confidence interval for one subject was calculated from the residual mean square of a two-way analysis of variance. For each parameter, the intersample variation differs according to the diagnosis. Confidence interval (risk = 5%) for one single subject reaches 29% for TBV in OP; 16% for TOS; 26% for TOV and TIOS in OM; 25% for TRS in ROD, and 69% in HPT, but is much lower for groups of 10 and 20 patients. These variations must be taken into account when successive biopsies are performed in one individual or in groups of patients to follow the course of a disease or evaluate the effects of a therapy.