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.

Electromyography in nutritional osteomalacic myopathy.

“…Disuse from pain contributes very little to the symptomatology and is, moreover, common to all osteomalacias. We strongly feel that, even though some of the clinical material used by Dastur et al (1975) and here is the same, the nature of muscular change in osteomalacia of nutritional aetiology is no different from that due to other causes. Osteomalacia regardless of its aetiology is in fact a true reversible myopathy, as noted by others earlier.…”

“…To date light microscopy and occasional reports of electronmicroscopy (Smith and Stern, 1969;Stern ct al., 1973) have shown no signifi- Dastur et al (1975) maintain that on electronmicroscopy they found 'evidence of non-specific muscular atrophy in the nutritional group and degenerative changes which constitute a form of myopathy similar to those seen in muscular dystrophies in the group with a major added metabolic or endocrinal factor'. They contend that in nutritional osteomalacia no myopathy exists and the proximal muscle weakness is in the nature of an atrophy, a reflection of a combination of disuse and malnutrition of the musculature.…”

Calcium and Vitamin D Status in Heart Failure Patients in Isfahan, Iran

“…Probable mechanisms may be: upregulation of pro-inflammatory and down-regulation of anti-inflammatory cytokines [7,8,18,19], overstimulation of the renin-angiotensin system [5,6], proliferation of smooth muscle cells, and atrophy, degeneration, and or proliferation of cardiomyocytes [11,20,21], defects in heart cell calcium metabolism through regulation of calcium channel activity mediated by the cAMP pathway [22], remodeling of heart extracellular matrix metabolism mediated by matrix metalloproteinases [23], secondary hyperparathyroidism with its cardiac consequences [9,10], and many other less well-appreciated ones. In our study, there was no direct correlation between serum 25(OH)D 3 and its deficiency with LVEF and NYHA functional class.…”

An unusual myopathy: Speckled muscle fibers due to enlarged mitochondria

“…Vitamin D deficiency, in association with the patient's history of low serum ferritin, suggests that the patient may have had a nutritional or absorption defect to account for her illness. Vitamin D deficiency causes myopathy, but on histopathology minimal changes such as atrophy are the only features to be seen 4. Alternatively, parathyroid hormone is known to regulate body levels of a number of ions including magnesium, sodium, potassium, and bicarbonate 12.…”