David W. Dempster

Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: comparison with transiliac bone biopsy

SummaryWe compared microarchitecture and mechanical competence parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite-element analysis of radius and tibia to those measured by histomorphometry, micro-CT, and finite-element analysis of transiliac bone biopsies. Correlations were weak to moderate between parameters measured on biopsies and scans.IntroductionHR-pQCT is a new imaging technique that assesses trabecular and cortical bone microarchitecture of the radius and tibia in vivo. The purpose of this study was to determine the extent to which microarchitectural variables measured by HR-pQCT reflect those measured by the “gold standard,” transiliac bone biopsy.MethodsHR-pQCT scans (Xtreme CT, Scanco Medical AG) and iliac crest bone biopsies were performed in 54 subjects (aged 39u2009±u200910xa0years). Biopsies were analyzed by 2D quantitative histomorphometry and 3D microcomputed tomography (µCT). Apparent Young’s modulus, an estimate of mechanical competence or strength, was determined by micro-finite-element analysis (µFE) of biopsy µCT and HR-pQCT images.ResultsThe strongest correlations observed were between trabecular parameters (bone volume fraction, number, separation) measured by µCT of biopsies and HR-pQCT of the radius (R 0.365–0.522; Pu2009<u20090.01). Cortical width of biopsies correlated with cortical thickness by HR-pQCT, but only at the tibia (Ru2009=u20090.360, Pu2009<u20090.01). Apparent Young’s modulus calculated by µFE of biopsies correlated with that calculated for both radius (Ru2009=u20090.442; Pu2009<u20090.001) and tibia (Ru2009=u20090.380; Pu2009<u20090.001) HR-pQCT scans.ConclusionsThe associations between peripheral (HR-pQCT) and axial (transiliac biopsy) measures of microarchitecture and estimated mechanical competence are significant but modest.

Issues in modern bone histomorphometry.

This review reports on proceedings of a bone histomorphometry session conducted at the Fortieth International IBMS Sun Valley Skeletal Tissue Biology Workshop held on August 1, 2010. The session was prompted by recent technical problems encountered in conducting histomorphometry on bone biopsies from humans and animals treated with anti-remodeling agents such as bisphosphonates and RANKL antibodies. These agents reduce remodeling substantially, and thus cause problems in calculating bone remodeling dynamics using in vivo fluorochrome labeling. The tissue specimens often contain few or no fluorochrome labels, and thus create statistical and other problems in analyzing variables such as mineral apposition rates, mineralizing surface and bone formation rates. The conference attendees discussed these problems and their resolutions, and the proceedings reported here summarize their discussions and recommendations.

Teriparatide for idiopathic osteoporosis in premenopausal women: A pilot study

CONTEXTnPremenopausal women with idiopathic osteoporosis (IOP) have abnormal cortical and trabecular bone microarchitecture.nnnOBJECTIVEnThe purpose of this study was to test the hypotheses that teriparatide increases bone mineral density (BMD) and bone formation and improves trabecular microarchitecture and stiffness in women with IOP.nnnDESIGNnThis was an open-label pilot study.nnnSETTINGnThe setting was a tertiary care referral center.nnnPATIENTSnParticipants were 21 premenopausal women with unexplained fragility fractures or low BMD.nnnINTERVENTIONnTeriparatide was administered at 20 μg daily for 18 to 24 months.nnnMAIN OUTCOME MEASURESnThe primary endpoint was within-subject percent change in lumbar spine BMD. Secondary endpoints included percent change in hip and forearm BMD, transiliac biopsy parameters (trabecular bone volume, microarchitecture, stiffness, and adipocytes), serum N-terminal propeptide of procollagen type 1 (P1NP), and C-telopeptide.nnnRESULTSnBMD increased at the spine (10.8 ± 8.3% [SD]), total hip (6.2 ± 5.6%), and femoral neck (7.6 ± 3.4%) (all P < .001). Serum P1NP doubled by 1 month, peaked at 6 months, and returned to baseline by 18 to 24 months. Transiliac biopsies demonstrated significant increases in cortical width and porosity and trabecular bone volume and number increased, mirrored by a 71% increase in trabecular bone stiffness (P < .02-.001). Adipocyte area, perimeter, and volume/marrow volume decreased, with no change in adipocyte number. Four women had no increase in BMD and a blunted, delayed increase in serum P1NP. Nonresponders had markedly lower baseline bone formation rate (0.002 ± 0.001 vs 0.011 ± 0.006 mm²/mm/y; P < .001) and higher serum IGF-1 (208 ± 54 vs 157± 44 ng/mL; P = .03).nnnCONCLUSIONSnTeriparatide was associated with increased spine and hip BMD and improved trabecular microarchitecture and stiffness at the iliac crest in the majority of women with IOP.

CHAPTER 26 – Histomorphometric Analysis of Bone in Primary Hyperparathyroidism

Bone histomorphometry allows accurate evaluation not only of bone mass and turnover but also of bone microarchitecture Microscopic examination of bone biopsied from the iliac crest after in vivo tetracycline labeling permits separate assessments of cortical and cancellous bone, a clear advantage over noninvasive methods of bone mass measurement, which can provide only indirect information in this regard. This technique has clinical applications in selected disorders— such as primary hyperparathyroidism, where it allows the detection of abnormalities of bone turnover, even in asymptomatic subjects showing no radiologic evidence of bone disease. In spite of limitations inherent in the small size of the biopsy sample and regional variations among skeletal sites, the iliac crest site is generally considered to represent both the structure and the metabolic processes that affect the entire skeleton. A histomorphometric study confirmed the accelerated rate of bone remodeling in primary hyperparathyroidism. In a group of subjects with mild primary hyperparathyroidism, there was a two to three fold increase in the values of static and dynamic turnover indices.

Marrow adiposity assessed on transiliac crest biopsy samples correlates with noninvasive measurement of marrow adiposity by proton magnetic resonance spectroscopy ( 1 H-MRS) at the spine but not the femur

SummaryMeasurement of marrow fat (MF) is important to the study of bone fragility. We measured MF on iliac biopsies and by spine/hip magnetic resonance spectroscopy in the same subjects. Noninvasively assessed spine MF and histomorphometrically assessed MF correlated well. MF quantity and relationships with bone volume differed by measurement site.IntroductionExcess marrow fat has been implicated in the pathogenesis of osteoporosis in several populations. In the bone marrow, adipocytes and osteoblasts share a common precursor and are reciprocally regulated. In addition, adipocytes may secrete toxic fatty acids and adipokines that adversely affect osteoblasts. Measurement of marrow fat is important to the study of mechanisms of bone fragility. Marrow fat can be quantified on bone biopsy samples by histomorphometry and noninvasively by proton magnetic resonance spectroscopy (1H-MRS). In this study, we evaluate relationships between marrow fat assessed using both methods in the same subjects for the first time.MethodsSixteen premenopausal women, nine with idiopathic osteoporosis and seven normal controls, had marrow fat measured at the iliac crest by bone biopsy and at the lumbar spine (L3) and proximal femur by 1H-MRS.ResultsAt L3, fat fraction by 1H-MRS correlated directly and significantly with marrow fat variables on iliac crest biopsies (ru2009=u20090.5–0.8). In contrast, there were no significant correlations between fat fraction at the femur and marrow fat on biopsies. Marrow fat quantity (%) was greater at the femur than at L3 and the iliac crest and correlated inversely with total hip and femoral neck BMD by DXA.ConclusionsIn summary, measurement of marrow fat in transiliac crest biopsies correlates with marrow fat at the spine but not the proximal femur by 1H-MRS. There were site-specific differences in marrow fat quantity and in the relationships between marrow fat and bone volume.