While osteoporosis is characterized by a low bone mass there is a well-recognized overlap in bone mineral density (BMD) measurements between groups of subjects with and without vertebral fracture. To investigate whether differences in trabecular architecture may contribute to the presence or absence of fractures independent of the bone mass, fracture and nonfracture groups matched for age, gender, and BMD were assembled. Transiliac biopsies and corresponding lumbar spine BMD measurements from 31 women and 16 men with vertebral fracture were compared with those from 22 women and 11 men without fracture. Lumbar BMD (L1-4) was measured using a Hologic 2000 densitometer. The lumbar BMD was similar in women with and without fracture (0.63 g/cm(3) +/- 0.10 SD and 0.71 g/cm(3) +/- 0.17 SD, n.s.) and in men with and without fracture (0.72 g/cm(3) +/- 0.12 SD and 0.76 g/cm(3) +/- 0.17 SD, n.s.). Undecalcified iliac crest biopsy sections, 8 microm thick, were analyzed for remodeling variables and trabecular architecture using OsteoMeasure and TAS image analysis systems. No significant difference was found in either gender between fracture and nonfracture groups in percent bone volume (mean 10% in all groups), or in the wide range of remodeling and architectural variables measured, including the trabecular width, number, and separation, mean trabecular plate density and fractal dimension, as well as several indirect indices of connectivity including the node:terminus ratio, marrow star volume, and trabecular pattern factor. On the basis of this evidence it was concluded that there is no difference in the trabecular architecture between patients with crush fracture and controls when account is taken of bone mass. This suggests that microanatomical disruption is a predictable intrinsic feature of bone loss. However, there remains the possibility that the two-dimensional character of the structural deterioration measured indirectly is not sufficiently sensitive for the complex cancellous system. This is considered further in part II.

Osteoporosis is a generic term implying a decrease in bone mass which increases the risk of fracture. It is now becoming appreciated that decreases in bone mass alone are not the sole factor in increasing the risk of osteoporotic fracture, and that other skeletal and extraskeletal factors also contribute significantly to this risk. Extraskeletal factors include the propensity to falls and responses to falls, whereas additional skeletal factors include bone turnover, the ability to repair fatigue damage and the tertiary structure of bone, particularly trabecular tissue. There are a large number of causes of secondary osteoporosis each with their own specific pathophysiological mechanisms. It is therefore not surprising that they have heterogeneous effects on the skeleton. A good example is provided in corticosteroid osteoporosis which is characterised by thinning of trabecular elements, whereas postmenopausal osteoporosis is characterised less by thinning and more by destruction of trabecular elements which derange trabecular continuity. A variety of techniques are now being developed to address the heterogeneity of trabecular osteoporosis. These include direct histomorphometric techniques to assess trabecular continuity, and indirect techniques such as the attenuation of ultrasound. These different pathophysiological mechanisms in osteoporosis have important therapeutic implications, particularly with agents that affect bone remodelling. Since bone remodelling is a surface-based phenomenon, if trabecular surfaces are destroyed, the augmentation of bone mass may thicken remnant structures without restoring trabecular continuity. Since most treatments for osteoporosis affect bone remodelling they are likely to have a greater effect in restoring structural integrity of the skeleton in corticosteroid than in postmenopausal osteoporosis.

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Pregnancy and lactation make demands on maternal calcium homeostasis which may affect bone strength. Recently, changes in cancellous architecture have been described in iliac crest bone biopsies from normal pregnant women but the rarity of such human material means an animal model is essential. The microanatomy of cancellous bone was compared in uniparous and multiparous rats using undecalcified histological sections of lumbar and caudal vertebrae and also proximal femora. An automated trabecular analysis system (TAS) measured a comprehensive range of structural variables including the trabecular number, connectivity and width. In the first pregnancy cycle an early stimulation of bone formation (which quadrupled at some sites) was indicated by an increase in the skeletal uptake and spacing of double calcein labels and the immediate generation of thicker more numerous and interconnected trabeculae. A 40 % increase in cancellous bone volume was observed in the lumbar spine in comparison with age-matched virgin controls. In contrast, a rapid succession of 3 pregnancy cycles (including lactation) culminated in cancellous atrophy of 15 % at the same site, with a loss in trabecular number ranging from 20 % (caudal vertebra) to 30 % (lumbar vertebrae). In comparison, the proximal femur lost 40 % of its struts but, nevertheless, uniquely sustained its cancellous bone volume. When lactation was excluded the number of struts lost was halved although trabecular thinning then took place which was sufficient to maintain the previous 15 % deficit in bone volume. It was concluded that a single pregnancy strengthens the cancellous component of the maternal skeleton while a quick succession of pregnancies weakens it. Lactation influences the pattern of bone loss but not its amount.