Does weight gain induce cortical and trabecular bone regain in anorexia nervosa? A two-year prospective study.

This prospective study examines bone density and structure over a two-year time period in women with anorexia nervosa (AN) under weight gain treatment. Twenty-four women with AN were examined at baseline and at two annual follow-up examinations. In 9 AN patients BMI increased whereas in 15 it remained unchanged or decreased. Dual energy X-ray absorptiometry (DXA) was performed on the lumbar spine, the femoral neck and the whole hip and three-dimensional peripheral quantitative computer tomography (3D-pQCT) was performed on the ultradistal radius. ANOVAs for repeated measures were used to examine change over time in BMI and bone parameters. At baseline, patients with increased BMI had significantly higher bone density of femoral neck and total hip, and higher levels in all 3D-pQCT parameters of the ultradistal radius, compared to the group with unchanged or decreased BMI. The two groups did not differ at baseline in bone density of the spine. ANOVAs showed that bone density of the total hip increased significantly and that overall bone density (D100), the density of the trabecular area (D.Trab.) and the cortical thickness (C.Th.) in the ultradistal radius decreased significantly. Group x time interactions showed that changes over time were different in the two groups with regard to spine density and in the parameters D100, D.Trab. and C.Th. of the ultradistal radius. In the group with increased BMI the spine density dropped at the first follow-up whereas at the second follow-up it rose again to baseline. Patients with unchanged or decreased BMI showed a small but steady increase in spine density. The group changes of D100, D.Trab. and C.Th. of the ultradistal radius all followed the same pattern. Bone mineral density at all locations measured with both technologies (DXA and 3D-pQCT) did not vary according to BMI changes. The course of bone density and structure at different locations was different, and, despite weight increase, bone regain appeared to need different time periods.

Noninvasive in vivo monitoring of bone architecture alterations in hindlimb-unloaded female rats using novel three-dimensional microcomputed tomography.

UNLABELLED: We tested a novel microcomputed tomograph designed to longitudinally and noninvasively monitor bone alterations in hindlimb-unloaded female rats at a resolution of 26 microm over a period of 3 weeks. This prototype has a potential to detect three-dimensional trabecular microarchitectural changes induced by growth and unloading. INTRODUCTION: Until now, data concerning structural changes of cancellous bone have only been available after necropsy of animals. In this study, we tested a novel microcomputed tomography (microCT) technique designed to monitor such changes repeatedly at a resolution of 26 microm with an acquisition time of about 10 minutes to map the entire proximal tibial metaphysis. MATERIALS AND METHODS: Four-month-old female Wistar rats were randomized to seven groups of 10 animals to be either tail-suspended or to act as controls. MicroCT and DXA measurements were performed at 0, 7, 14, and 23 days in suspended and control rats. One group was killed at each of these time points, and bone samples were processed for histomorphometry and ex vivo microCT. RESULTS: We verified that a good correlation was obtained between two-dimensional bone parameters evaluated in longitudinal tibial sections either by histomorphometry or microCT and microCT parameters obtained from either in vivo or ex vivo tibias. The longitudinal survey allowed earlier detection of both growth and unloading-related bone changes than the transverse survey. In controls, aging induced denser bones, reorganization of the trabecular network toward a more oriented plate-like structure, and an isotropic pattern. Unloading first inhibited cortical and cancellous bone growth and then induced bone loss characterized by fewer trabeculae, reduced connectivity density, and enhanced structure model index (SMI), revealing a lighter cancellous structure with development of rod-like characteristics. CONCLUSION: We show for the first time that this microCT prototype has a great potential to accurately, repeatedly, reliably, and rapidly investigate alterations of three-dimensional trabecular microarchitecture.

Tail suspension induces bone loss in skeletally mature mice in the C57BL/6J strain but not in the C3H/HeJ strain.

We assessed the effects of tail-suspension in two skeletal genetic backgrounds, the high C3H/HeJ (C3H) and low C57BL/6J (B6) bone masses inbred mice (male, 4-months old). Cancellous bone mass and structural parameters were evaluated in distal femoral metaphysis by three dimensional microcomputed tomography. Bone cellular activities were evaluated by histomorphometry and measurements of alkaline phosphatase activity (ALP) and osteocalcin in blood and deoxypyridinoline (D-pyr) in urine. In C3H mice, 2- and 3-week unloading experiments were performed. After an early and transient decrease in body weight, a 2-week suspension period resulted in stimulation of both bone formation rate by 45% and active osteoclastic surfaces by 19%. D-pyr did not change, but ALP and osteocalcin levels increased by 18% and 72%, respectively, in 2-week suspended mice, and osteocalcin remained elevated by 30% in the 3-week suspended mice. Such cellular modifications allowed the C3H mice to maintain their initial bone mass and trabecular structural parameters even after a 3-week suspension period. In B6 mice, 1- and 2-week unloading experiments were performed. Tail suspension resulted in decreased body weight during the first days followed by an incomplete recovery during the second week of unloading. The resorption activity was unaffected by any suspension time period, whereas a decrease of 42.5% in bone formation rate and of 21.5% in ALP were seen by the end of the first week of suspension, both values being restored after a 2-week suspension period. At this latter time, trabeculae were thinner, leading to a 24.5% cancellous bone loss. Trabecular number and connectivity, rod-plate index, and degree of anisotropy were not modified. We concluded that C3H mice constituted a unique model in which genetic background overwhelmed the usual effects of reduced biomechanical usage in bone, whereas B6 mice, compared with the standardized rat model, offered an alternative model of bone loss in a mature skeleton.

Are patterns of bone loss in anorexic and postmenopausal women similar? Preliminary results using high resolution peripheral computed tomography.

This study intended to compare bone density and architecture in three groups of women: young women with anorexia nervosa (AN), an age-matched control group of young women, and healthy late postmenopausal women. Three-dimensional peripheral quantitative high resolution computed-tomography (HR-pQCT) at the ultradistal radius, a technology providing measures of cortical and trabecular bone density and microarchitecture, was performed in the three cohorts. Thirty-six women with AN aged 18-30 years (mean duration of AN: 5.8 years), 83 healthy late postmenopausal women aged 70-81 as well as 30 age-matched healthy young women were assessed. The overall cortical and trabecular bone density (D100), the absolute thickness of the cortical bone (CTh), and the absolute number of trabecules per area (TbN) were significantly lower in AN patients compared with healthy young women. The absolute number of trabecules per area (TbN) in AN and postmenopausal women was similar, but significantly lower than in healthy young women. The comparison between AN patients and post-menopausal women is of interest because the latter reach bone peak mass around the middle of the fertile age span whereas the former usually lose bone before reaching optimal bone density and structure. This study shows that bone mineral density and bone compacta thickness in AN are lower than those in controls but still higher than those in postmenopause. Bone compacta density in AN is similar as in controls. However, bone inner structure in AN is degraded to a similar extent as in postmenopause. This last finding is particularly troubling.

Two-week longitudinal survey of bone architecture alteration in the hindlimb-unloaded rat model of bone loss: sex differences.

The goal of this study was to determine, through a longitudinal follow-up, whether sex influences bone adaptation during simulated weightlessness. Twelve-week-old male and female Wistar rats were hindlimb unweighted for 2 wk, and the time course of bone alteration was monitored in vivo by means of densitometry and unbiased three-dimensional quantitative microcomputed tomography at 7 and 14 days. Compared with male rats, female rats had twice more cancellous bone volume at the proximal tibia at baseline, and this bone volume continued to increase, whereas in males it stabilized. Conversely, cortical area was greater in males than in females, and in both sexes cortical bone was still expanding. Hindlimb unloading resulted in larger reductions in males than in females in both cortical and cancellous compartments. In females, trabecular thickness and number decreased mildly, whereas in males trabecular number was dramatically reduced. In both sexes, the trabecular network became less connected and more rod-like shaped. Bone cellular activities evaluated by histomorphometry showed decreased bone formation rate in both sexes and increased resorption activity only in males. In conclusion, in female rats unloaded-related cancellous alterations reversed the growing process, whereas in males, which show lower growth process, it induced an accentuation of age-related cancellous bone changes for most of the parameters.

Cortical and trabecular bone density and structure in anorexia nervosa.

The aim of the study was to examine bone density and architecture with three different measurement methods in a sample of young women with anorexia nervosa (AN) and in an age-matched control group of women. Three-dimensional periphery quantitative computer tomography (3D-pQCT) at the ultradistal radius, a new technology providing measures of cortical and trabecular bone density and architecture, was performed, as well as quantitative ultrasound (QUS) at the heel, and dual energy X-ray absorptiometry (DXA) at the spine and hip. Thirty-six women with AN aged 18-30 years (mean duration of AN: 5.8 years) and 30 age-matched women were assessed. Bone mineral density measured by DXA at the spine and hip, and broadband ultrasound attenuation measured by QUS at the heel were significantly lower in patients than controls. 3D-pQCT demonstrated a highly significant deficit in the absolute number of bone trabecules and a significant reduction of cortical thickness. Severity of underweight was significantly associated with bone deficits at the hip measured by DXA. 3D-pQCT revealed mostly deficits of cortical bone related with age of onset of eating disorder. Using three different methods to measure bone density and bone structure at the hip, spine, heel and ultradistal radius, significant deficits in bone mineral density both in trabecular and cortical bone, as well in trabecular structure could be demonstrated in the AN patients.

Quantification of Bone Microarchitecture with the Structure Model Index.

The deterioration of cancellous bone structure due to aging and disease is characterized by a conversion from plate elements to rod elements. Consequently the terms "rod-like" and "plate-like" are frequently used for a subjective classification of cancellous bone. In this work a new morphometric parameter called Structure Model Index (SMI) is introduced, which makes it possible to quantify the characteristic form of a three-dimensionally described structure in terms of the amount of plates and rod composing the structure. The SMI is calculated by means of three-dimensional image analysis based on a differential analysis of the triangulated bone surface. For an ideal plate and rod structure the SMI value is 0 and 3, respectively, independent of the physical dimensions. For a structure with both plates and rods of equal thickness the value lies between 0 and 3, depending on the volume ratio of rods and plates. The SMI parameter is evaluated by examining bone biopsies from different skeletal sites. The bone samples were measured three-dimensionally with a micro-CT system. Samples with the same volume density but varying trabecular architecture can uniquely be characterized with the SMI. Furthermore the SMI values were found to correspond well with the perceived structure type.