title: Nature of muscular change in osteomalacia: light- and electron-microscope observations.
abstract: Thirteen muscle biopsy specimens (mainly the gluteus maximus) from 12 patients with laboratory confirmation of osteomalacia and proximal muscle weakness in 10 were examined by light and electron microscopy. Light microscopy revealed mild diffuse non-specific atrophy of the muscle fibres in 10 cases, severe generalised atrophy in one and patchy group atrophy in one. There was no myopathic change in specimens from cases with either a nutritional aetiology, or a mixed aetiology. The former, mostly women gave a history of severe chronic malnutrition often accompanied by repeated pregnancies and prolonged lactation; those with a mixed aetiology gave, in addition, evidence of a metabolic or endocrine disorder such as hyperparathyroidism, hyperthyroidism, uraemia, or treatment with anti-epileptic drugs or were of uncertain origin. Electron-microscope examination of muscle from the nutritional group showed atrophic changes in the fibres, such as loss of myofibrils, prominence of mitochondria and glycogen, loosening and folding of the basement-membrane but good preservation of the remaining myofibrils. In contrast muscle from cases of mixed aetiology showed, in addition to the atrophic features, clear degenerative changes in the myofibrils and the mitochondria, accumulation of amorphous material at the site of myofibrillar loss and of lipofuscin in muscle fibres, vascular endothelium and satellite cells. The earliest degenerative change was in the "I" band, involving actin filaments and "Z" line. The triads were generally preserved but the sarcoplasmic reticulum appeared affected in a patient with tetany and severe mitochondrial degeneration. In a patient with thyrotoxicosis, proliferation of central nuclei, "Z" line streaming and formation of "T" tubular aggregates were seen. In one patient with hyperparathyroidism and hypercalcaemia, severe myofibrillar degeneration and mitochondria showing osmiophilic deposits, possibly of calcium phosphate, were encountered. It is concluded: (1) that all osteomalacic muscle weakness is not myopathic but a non-specific atrophy occurring probably on the basis of disuse and malnutrition, and (2) patients with an added metabolic or endocrinological disorder show in addition to the atrophy, degenerative changes in the muscle fibre and its sub-cellular components consistent with myopathy, and these patients should be clearly distinguished from those with a background of malnutrition only.
mesh_terms: D000293:Adolescent; D000328:Adult; D001485:Basement Membrane / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000150:complications; D006961:Hyperparathyroidism / Q000150:complications; D006980:Hyperthyroidism / Q000150:complications; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000648:ultrastructure; D009132:Muscles / Q000648:ultrastructure*; D009133:Muscular Atrophy / Q000473:pathology; D009210:Myofibrils / Q000648:ultrastructure; D009748:Nutrition Disorders / Q000150:complications; D010018:Osteomalacia / Q000150:complications / Q000473:pathology*; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure; D014808:Vitamin D Deficiency / Q000150:complications