J Dequeker

Interim report and recommendations of the World Health Organization Task-Force for Osteoporosis.

Harry K. Genant (Chairman) , Cyrus Cooper (Rapporteur) , Gyula Poor (Rapporteur) , Ian Reid (Rapporteur) , George Ehrlich (Editor), J. Kanis (Editor), B. E. Christopher Nordin (Editor), Elizabet h Barrett-Connor , Dennis Black, J.-P. Bonjour, Bess Dawson-Hughes , Pierre D. Delmas, J. Dequeker , Sergio Ragi Eis, Carlo Gennari , Olaf Johnell , C. Conrad Johnston, Jr, Edith M. C. Lau, Uri A. Liberman, Robert Lindsay, Thomas John Martin, Basel Masri, Carlos A. Mautalen, Pierre J. Meunier, Paul D. Miller , Ambrish Mithal, Hirotoshi Morii , Socrates Papapoul os, Anthony Woolf, Wei Yu and Nikolai Khaltaev (WHO Secretariat) 30

Prediction of vertebral strength in vitro by spinal bone densitometry and calcaneal ultrasound

Spinal bone mineral density (BMD) measurements and calcaneal ultrasound were compared in terms of their ability to predict the strength of the third lumbar vertebral body using specimens from 62 adult cadavers (28 females, 34 males). BMD was measured using dual X‐ray absorptiometry (DXA) in both vertebra and calcaneus. Quantitative computed tomography (QCT) was used to determine trabecular BMD, cortical BMD, cortical area, and total cross‐sectional area (CSA) of the vertebral body. Bone velocity (BV) and broadband ultrasonic attenuation (BUA) were measured in the right calcaneus. Vertebral strength was determined by uniaxial compressive testing. Vertebral ultimate load was best correlated with DXA‐determined vertebral BMD (r2 = 0.64). Of the QCT parameters, the best correlation with strength was obtained using the product of trabecular BMD and CSA (r2 = 0.61). For vertebral ultimate stress, however, the best correlation was observed with QCT‐measured trabecular BMD (r2 = 0.51); the correlation with DXA‐determined BMD was slightly poorer (r2 = 0.44). Calcaneal ultrasound correlated only weakly with both ultimate load and stress with correlation coefficients (r2) of 0.10–0.17, as did calcaneal BMD (r2 = 0.18). Both spinal DXA and spinal QCT were significantly (p < 0.001) better predictors of L3 ultimate load and stress than were either calcaneal ultrasound or calcaneal DXA. Multiple regression analysis revealed that calcaneal ultrasound did not significantly improve the predictive ability of either DXA or QCT for L3 ultimate load or stress. Calcaneal DXA BMD, bone velocity, and BUA correlated well with each other (r2 = 0.67–0.76), but were only modestly correlated with the DXA and QCT measurements of the vertebra. These data indicate that spinal DXA and spinal QCT provide comparable prediction of vertebral strength, but that a substantial proportion (typically 40%) of the variability in vertebral strength is unaccounted for by BMD measurements. Ultrasonic measurements at the calcaneus are poor predictors of vertebral strength in vitro, and ultrasound does not add predictive information independently of BMD. These findings contrast with emerging clinical data, suggesting that calcaneal ultrasound may be a valuable predictor of vertebral fracture risk in vivo. A possible explanation for this apparent discrepancy between in vivo and in vitro findings could be that current clinical ultrasound measurements at the calcaneus reflect factors that are related to fracture risk but not associated with bone fragility.

Long-Term Changes in Bone Mineral and Biomechanical Properties of Vertebrae and Femur in Aging, Dietary Calcium Restricted, and/or Estrogen-Deprived/-Replaced Rats

To study the long‐term effect of aging, low calcium diet (LCD) and/or ovariectomy (OVX), and estrogen replacement therapy (+E) on rat bone quality of both trabecular and cortical bone, 150 female Wistar rats of 4.5 months were divided into baseline, sham‐operation (sham), sham + LCD, OVX, OVX + E, OVX + LCD, OVX + LCD + E, and were observed for 3, 6, and 9 months postsurgery. The bone mineral density (BMD) of the lumbar spine L1–L4, the femoral neck, the midshaft, and the distal metaphysis were determined using dual‐energy X‐ray absorptiometry (DXA) in vitro. Biomechanical tests of the L1 vertebral body and the left femur were performed. The right femoral midshaft and neck were processed undecalcified for determining cross‐sectional moments of inertia (CSMIs). BMD in all groups increased rapidly with aging in the femoral midshaft composed only of cortical bone at 3 months post‐OVX and stabilized or decreased thereafter, but decreased at all observation periods in the distal femoral metaphysis, consisting mostly of trabecular bone. L1 maximum compressive strength and stiffness increased as a function of aging in sham and sham + LCD but not in OVX and OVX + LCD. The order of loss in BMD at all sites and in L1 strength and stiffness was: OVX + LCD > OVX > LCD. LCD reduced while OVX improved the total femoral area, CSMIs in the femoral midshaft, and the torsional strength. Estrogen treatment preserved BMD and prevented OVX‐induced loss in L1 strength. The BMD and biomechanical properties were greater in OVX + E than in OVX + LCD + E. Loss in BMD and CSMIs was greater in the femoral neck than in the midshaft. The data suggest that rat cortical bone might not be matured until 7.5 months of age. It would be more appropriate to consider rats at peak bone mass as a model of mature rat and to perform OVX at that time. LCD and OVX have a great potential for weakening the bone quality of cortical bone and trabecular bone, respectively, and have an additive effect when combined. Estrogen prevents only OVX‐induced bone loss.

Prediction of Vertebral and Femoral Strength In Vitro by Bone Mineral Density Measured at Different Skeletal Sites

The aim of the present study was to investigate the prediction of vertebral and femoral strength in vitro by bone mineral density (BMD) measured at different skeletal sites. The third lumbar vertebral body, the right proximal femur, and the right calcaneus were removed from 38 male and 32 female cadavers (mean age 69 years, range 23–92 years). Areal BMD of all bone specimens was determined by dual‐energy X‐ray absorptiometry (DXA). The failure load of the vertebral body and the femur was determined by mechanical testing. Vertebral and femoral strength were both greater in males than females (p < 0.01), as was BMD at all sites (p < 0.01). Vertebral strength correlated well with vertebral BMD (r2 = 0.64) but was only moderately correlated with BMD measured at the femur (r2 = 0.36) or the calcaneus (r2 = 0.18). Femoral strength showed the highest correlations with femoral BMD (r2 = 0.88) and somewhat weaker relationships with BMD at the vertebra (r2 = 0.50) and the calcaneus (r2 = 0.54). BMD values at the vertebra, femur, and calcaneus were only moderately interrelated (r2 = 0.31–0.65), and vertebral strength correlated only modestly with the strength of the femur (r2 = 0.36). These in vitro results support the concept that optimal prediction of vertebral or femoral strength by DXA requires site‐specific assessments.

Effects of anteversion on femoral bone mineral density and geometry measured by dual energy x-ray absorptiometry : A cadaver study

The effect of femoral neck anteversion on bone mineral density (BMD) and geometry as measured by dual energy X-ray absorptiometry (DXA) was assessed using 64 right proximal femora from 36 male and 28 female cadavers. The anteversion angle was measured on computed tomography (CT) images, and DXA measurements were made both in the neutral position (i.e, at 0 degree anteversion, femoral neck axis parallel to the table) and in the simulated anteverted position (i.e., femoral shaft axis parallel to the table, greater and lesser trochanters in contact with the table, and femoral neck free). The mean anteversion angle measured by CT was 19.3 degrees (range 6 degrees-38 degrees). Anteversion was associated with a significant elevation in femoral neck BMD of +2.8% (range -5.3%-(+)9.8%) (p < 0.05), and the femoral neck BMD increased with increasing anteversion (p < 0.01). Trochanteric BMD was less affected by anteversion, with an average increase of only 0.2% (range -5%-5.9%) (p = n.s.) in the anteverted position, but there was a significant positive association between the change in trochanteric BMD and the anteversion angle (p < 0.01). Anteversion produced a mean reduction of -2.4% (range -7.6%-(+)4.3%) (p < 0.001) in apparent femoral neck axis length, while femoral neck width remained generally unaffected. These data confirm that femoral BMD as measured by DXA is affected by femoral anteversion with a lesser magnitude than previously reported. The use of trochanteric BMD may minimize the influence of anteversion. While the mean changes in BMD and neck axis length attributable to anteversion are modest, the considerable interindividual variability in the magnitude of the effects demonstrates that other factors, such as, the complex geometry of femoral neck modifies the effect of anteversion on BMD measurements. The error in BMD introduced femoral anteversion may represent a significant confounding influence in cross-sectional and longitudinal studies. Careful repositioning of the foot and leg is essential in monitoring changes in BMD longitudinally. Knowledge of the effects of femoral anteversion may assist in understanding the relation of femoral BMD and neck axis length to hip fracture.

EFFECTS OF LOW-DOSE LONG-TERM SODIUM FLUORIDE PREVENTIVE TREATMENT ON RAT BONE MASS AND BIOMECHANICAL PROPERTIES

Effects of fluoride on bone strength and cortical bone mass remain controversial. We compared 9-month, low-dose sodium fluoride (NaF) treatment with estrogen replacement therapy. Female Wistar rats 4.5 months old were divided into baseline, sham-operated (sham), sham-treated with NaF at 0.5 mg NaF/kg/day in drinking water, and ovariectomy (OVX), OVX treated with NaF and with estrogen. Bone mass was measured by dual X-ray absorptiometry (DXA)in vitro. Dimensions of the first lumbar vertebral body (L1) were determined by radiogrammetry. The right femur was processed undecalcified to obtain a midshaft cross-section to determine cross-sectional moments of inertia (CSMIs). L1 compressive test and left femoral torsional test were performed. OVX induced significant bone loss in L1 and femoral midshaft. Bone mass was increased to a greater extent in NaF-treated rats than in rats receiving estrogen replacement therapy. Femoral CSMIs in OVX rars, both L1 sizes and femoral CSMIs in NaF-treated rats, were significantly increased. Estrogen treatment had the least dimension expansion. OVX significantly decreased L1 compressive variables. There was no statistical difference in compressive parameters between NaF-treated groups and controls. OVX significantly increased femoral torsional strength but NaF treatment did not. Bone fluoride content was significantly increased after treatment with NaF. No significant difference in bone mineralization degree (ash and calcium) was found between treated and control rats. The discrepancy that an increase in bone mass and geometric properties in both trabecular and cortical bones by low-dose, long-term NaF treatment did not increase vertebral strength nor proportionally improve femoral strength indicated that the bone intrinsic biomechanical properties could be changed by NaF treatment.

Bone Mineral Density and Biomechanical Properties of Spine and Femur of Ovariectomized Rats Treated With Naproxen

Prostaglandins have been reported to mediate the effects of ovariectomy on bone loss. We studied the effect of naproxen, an inhibitor of production of prostaglandins, on ovariectomy-induced bone loss. One hundred forty female Wistar rats 4.5 months of age were divided into groups of baseline, sham operation (sham), sham treated with naproxen at 10 mg/kg per day (in food), and ovariectomy treated with naproxen or estrogen as intramuscular injection of estradiol at 0.2 mg/kg body weight per week. They were killed 3, 6, and 9 months postsurgery. Bone mineral density (BMD) of the lumbar spine (L1-4), femoral neck, midshaft, and distal metaphysis was determined using dual-energy X-ray absorptiometry (DXA) in vitro. The compressive test of the L1 vertebral body and torsional test of the left femur were performed. The right femoral neck and femoral midshaft were processed undecalcified for determining cross-sectional moments of inertia. Naproxen treatment partially prevented ovariectomy-induced loss or less gain in BMD, in a significant manner, in the femoral neck cortical area, and also in L1 compressive strength and stiffness. Estrogen fully prevented these ovariectomy-induced effects. Naproxen showed no effect on ovariectomy-induced improvement in femoral torsional strength and stiffness and cross-sectional moments of inertia. No statistically significant difference was found between naproxen-treated sham rats and untreated sham rats. The data suggest that naproxen partially prevents ovariectomy-induced osteopenia.

Plasma proteins in human cortical bone: enrichment of alpha 2 HS-glycoprotein, alpha 1 acid-glycoprotein, and IgE.

SummaryHuman cortical bones were extracted with EDTA, and the residue after EDTA extraction was digested with bacterial collagenase. Ten plasma proteins were identified and quantitated in the EDTA extracts. Three of them—IgE, IgD, andα1acid-glycoprotein—had not previously been described in bone or dentine. Five plasma proteins identified in collagenase digests are albumin, IgG, IgA, IgE, andα1acid-glycoprotein. IgE,α1acid-glycoprotein, andα2HS-glycoprotein were found to be concentrated in the bone more than other plasma proteins by factors between 11 and 525. The identification of plasma proteins was facilitated by the addition of polyethylene glycol in agarose gel. The presence of plasma proteins both in EDTA extracts and in collagenase digests suggests their structural role in bone.

Multicentre European COMAC-BME study on the standardisation of bone densitometry procedures

26 European centres participated in a concerted research action Biomedical Engineering: Quantitative Assessment of Osteoporosis. With a newly designed European spine and forearm phantom, the stability, accuracy, precision of dual energy absorption (DXA) and quantitative computer tomography (QCT) densitometry machines have been evaluated. Marked and clinically significant differences were found between brands and between techniques. Cross-calibration formulae have been made and normative data evaluated for different regions (spine, femoral neck, femoral trochanteric and forearm). A general fit for all data obtained from different machines was established.The cross-calibration formulae will allow a sensitivity analysis to assist the choice of equipment for clinical management of different categories of patients with bone disease. The present results obtained with an internationally accepted European spine and forearm phantom can now serve to stimulate the manufacturers to improve the comparability of bone measurements between machines.

Vertebral crush fracture syndrome and reflex sympathetic dystrophy

The association of reflex sympathetic dystrophy in one or more extremities with vertebral crush fracture syndrome is reported in six cases. In two of them the reflex sympathetic dystrophy preceded the vertebral crush fractures. The 99mTc-methylene diphosphonate scintigraphy results of the skeletons of 42 consecutive patients suffering from vertebral collapse and of 30 matched controls without osteoporosis have been evaluated by three independent observers for abnormal uptakes in the extremities. An abnormal radioactive bone tracer uptake in the extremities has been observed in 15 osteoporotics (36%) and 8 controls (29%). In most cases, osteoporotics and controls, the abnormal uptake was of the zonal type in a localized area, probably reflecting bone remodeling due to localized degenerative changes. An abnormal uptake of the segmental type involving multiple joints and even multiple extremities, as seen in reflex sympathetic dystrophy, was observed in 7 patients of the osteoporotic group (17%) and in none of the control group (P less than 0.05). The patients with an abnormal segmental uptake were younger and had a significantly higher mean 24 h calcium:creatinine ratio as well as a higher urinary hydroxyproline excretion. These observations and results suggest that in some cases of idiopathic osteoporosis there might be a relation between reflex sympathetic dystrophy and vertebral crush fracture syndrome, the vertebral crush fracture syndrome being the axial type of reflex sympathetic dystrophy.