J.R. Zanchetta

Mechanical validation of a tomographic (pQCT) index for noninvasive estimation of rat femur bending strength

Cross-sectional moment of inertia (CSMI) and volumetric cortical bone mineral density (vCtBMD) were assessed by peripheral quantitative computed tomography (pQCT) at femur midshafts from 103 Wistar female rats receiving 0 (n = 12) or 15-1000 mu g/kg/day sc of dexamethasone (n = 46) from 5 to 9 weeks of age, or 0 or 80 mg/kg 3/wk of AI(OH)(3) IP (n = 23,22) from 4 to 10 months of age. A bone strength index (BSI), calculated as the product CSMI x vCtBMD, was found to closely correlate (r = 0.94, R(2) = 0.89, p < 0.001) with the actual, mechanically tested bending breaking force of all bones. Correlation and determination coefficients obtained were higher than those usually reported employing different long-bone strength predictive formulae. The curve approached the origin and was linear throughout the wide range of CSMI, vCtBMD and BSI achieved because of age- and treatment-induced differences, showing a very low standard error of the estimate. Instead, different curve slopes and/or intercepts were found in separate analysis between data from each of the experiments when breaking force was correlated with CSMI or vCtBMD alone, or with the DEXA-assessed BMD of the mechanically assayed bone portion. Results suggest that noninvasive assessment of the BSI by means of pQCT technology provides an original tool for a precise and accurate estimation of long-bone bending strength that can be advantageously applied in crosssectional as well as longitudinal, in vivo studies employing animal models.

Bone mass in children: normative values for the 2-20-year-old population.

Normative values for bone mass were assessed for whole body bone mineral content (WBBMC), anterior-posterior and lateral lumbar spine, radius, femoral neck, trochanter, and Wards triangle bone mineral density in 778 healthy children and adolescents (433 females and 345 males) from 2-20 years of age from Argentina. Bone mineral content was assessed by dual energy X-ray absorptiometry (DEXA) (Norland XR-26 HS with dynamic filtration). All subjects were Caucasian. WBBMC maximum mean value for girls was found to be in the 16-year-old group with difference between gender becoming significant in the 17-year-old (p < 0.05) group. The femoral neck, trochanter, and Wards triangle BMD values in females increased until 14 years of age, with no significant difference between age groups older than 13. In males, no difference between age groups was seen in groups older than 16 years of age. The radius BMD showed a mild increment through infancy and adolescence in boys and girls. In lumbar spine, the gender differences were significant only in those groups over 16 years old, with boys showing a greater BMD than girls (p < 0.001). When Tanner stage was considered, the anova analysis showed in males that there were significant differences between stages (1-2, 2-3, and 4-5 (p < 0.01), but no differences between stages 3-4 for all the sites. In females, there were significant differences between stages 1-2 and 2-3 (p < 0.01), but not between stages 3-4 and 4-5 for WBBMC, FNBMD and LSBMD.(ABSTRACT TRUNCATED AT 250 WORDS)

LUMBAR SPINE BONE DENSITY IN ARGENTINE CHILDREN

It has been demonstrated that bone mineral density (BMD) in children and adolescents is influenced by individual height. The aim of the present work was to introduce a formula to include height in the BMD analysis. Postero-anterior (PA) (L2–L4) and lateral (L2–L3) lumbar BMD was assessed by dual X-ray absorptiometry (DXA) in 433 and 393, respectively, healthy Caucasian females from 2 to 20 years of age. A complete medical examination including weight, height, and Tanner puberal stage was performed in all the subjects. Bone age was assessed by left wrist radiographs and analyzed by the TW2 method to insure that it was within 1 year of chronological age. Bone mineral density adjusted for height (BMDcorr=BMC/projected area × height), was calculated for each individual. As analyzed by Tanner stage, both PA and lateral BMD increased up to stage 3, and there were no significant differences among stages 3–5. Results of BMDcorr variations related to Tanner stage suggested that the increase in lateral BMD before puberty might be related to height. PA BMDcorr increased up to Tanner stage 3, and there were no differences among stages 3–5. The BMDCORR approach can be used to get a more reliable analysis of BMD studies in children and adolescents.

Determination of femur structural properties by geometric and material variables as a function of body weight in rats. Evidence of a sexual dimorphism.

Femur diaphyses of male and female Wistar rats were densitometrically and biomechanically assayed. The BMD-dependent material properties were better in female than in male bones, but cross-section geometric properties were better in male femurs. As a result, mechanical properties of the integrated diaphyses were better in males, but differences disappeared after statistical adjustment of data to a common body weight. Results evidence a feed-back mechanism locally controlling the strain-dependent bone modelling and the corresponding cross-sectional design as related to bone stiffness, with a set-point adjusted to animal biomass. A sexual dimorphism of bone biomechanics is also described for the species.

Effects of on/off anabolic hPTH and remodelling inhibitors on metaphyseal bone of immobilized rat femurs. Tomographical (pQCT) description and correlation with histomorphometric changes in tibial cancellous bone

An anabolic effect of hPTH(1-38) (s.c. doses of 200 micrograms/kg/d during 75 days) on trabecular and cortical bone mass is tomographically described in the metaphyseal region of immobilized rat femurs using pQCT technology, in agreement with previous histomorphometrical studies of the proximal tibial metaphyses. Correlations between pQCT and histomorphometrical data showed that this effect derived from a stimulation of endosteal and trabecular bone modeling that induced a transference from trabecular to cortical bone mass. Loss of effects after withdrawal, resulting from a stimulation of bone remodeling, could be total or partially prevented by subsequent s.c. injections of risedronate (5 micrograms/kg/2/wk), 17-B-estradiol (10 micrograms/kg/d) or calcitonin (10 micrograms/kg/d) given during 60 days, in this order of effectiveness. The preventive potency was proportionally related to the reduction induced in histomorphometric indices of bone resorption.

TOMOGRAPHIC (pQCT) AND BIOMECHANICAL EFFECTS OF hPTH(1-38) ON CHRONICALLY IMMOBILIZED OR OVERLOADED RAT FEMURS

Six-month old rats chronically submitted to right hindlimb immobilization (IM) with mechanical overload (OL) of the left leg were treated 1 month later with 200 micrograms/kg/d of hPTH(1-38) for 15 or 75 days. Peripheral quantitative computed tomography (pQCT) scans and bending tests showed that hPTH increased cortical mass and volumetric BMD (vCtBMD) in both legs. However, elastic modulus of cortical bone and diaphyseal load-bearing capacity were improved only in OL bones. Improvement of diaphyseal strength was attributable to that of cortical bone quality, yet a stronger mechanostatic response of cortical modeling to bone material quality was also observed in treated OL bones. Data support hPTH(1-38) use for improving cortical bone mass and strength and point out a physical activity interaction with therapeutic results.

Intravenous olpadronate restores ovariectomy-affected bone strength. A mechanical, densitometric and tomographic (pQCT) study

Female Wistar rats aged 3 months were ovariectomized (OX, n = 27). Three months later they were given i.v. doses of 150 (6), 300 (7), or 600 (6) ug/kg 2/wk of olpadronate during 12 weeks or left as OX controls (OXc). Bending fracture load of femur diaphyses, reduced in OXc, was recovered by olpadronate. This effect was paralleled by changes in material quality indicators as DEXA-BMD, tomographic (volumetric) BMD, elastic modulus, and maximum elastic stress of cortical bone. No changes were induced by any of the treatments on cross-sectional area or moment of inertia. Diaphyseal stiffness, not reduced by OX, was enhanced to overnormal values by olpadronate at any dose. None of the treatments affected the normal mechanostatic interrelationships between cross-sectional architecture and bone material quality indicators. The positive effects described point out important differences in bisphosphonate action on bone biomechanics according to the experimental conditions assayed.

Monophasic dose-response curves of betamethasone on geometric and mechanical properties of femur diaphyses in growing rats

The biomechanical repercussion of the corticoid-induced osteopenia (a severe consequence of long-term glucocorticoid therapy) was studied in cortical bone of small rodents. Growing rats receiving 12.5-3200 micrograms/kg/d of betamethasone (BMS) s.c. for 20 days suffered a log-dose related impairment in body weight gain and in mechanical (fracture load, bending stiffness) and cross-sectional properties (area, moment of inertia) of femur diaphyses. No changes in bone material properties (ability to stand stress, elastic modulus, energy absorption per unit volume) were observed. At variance with the biphasic dose-response curves (positive effects at low-medium doses, negative at high doses) previously obtained with cortisol in a similar model, only negative effects on every variable studied were observed in this experiment. Results suggest that BMS effects on cortical bone biomechanics derived mainly or completely from those induced on bone geometry (biomechanical correlate of corticoid-induced osteopenia) in the assayed conditions. Data are compatible with a BMS-induced change in the setpoint of bone mechanostat. Correlation of bone geometric and biomechanical data with body weight gain showed that the anti-anabolic effects of BMS on bone were proportionally less intense than those exerted on the whole biomass.

Effects of risedronate given alone or after anabolic hPTH(1-38) on immobilized or overloaded rat tibiae and femora. A tomographic (pQCT) and histomorphometric study

E T I D R O N A T E V E R S U S S O D I U M F L U O R I D E IN POSTMENOPAUSAL OSTEOPOROSIS, N. Guaf labens 1, J . F a r r e r o n s z, L. Perez-Edo ~, A, Monegal 1, A. R e n a u ~, M. Roea 1, M. Pavea i 4, J . Carbonel l 3, Metabolic Bone Diseases Uni t , Hospi ta l Clinic 1, Serv ice o f In t e rna l Medicine. Hosp. Santa Creu i Sent Pau z. Service of Rheumato logy Hosp . N . S . E s p e r a n q a 3. I .M. t .M. ~.