SYNOPSISThe histopathology of bone is described in 60 patients with chronic renal failure due to a variety of renal diseases. Changes of azotaemic renal osteodystrophy included osteitis fibrosa, osteomalacia, and osteosclerosis. Quantitative histology using a point-counting technique revealed a significant increase in total bone, mineralized bone, and osteoid in comparison with a control group of 68 individuals. Osteitis fibrosa due to secondary hyperparathyroidism occurred in 93 %, osteomalacia in 40%, and osteosclerosis in 30% of patients. Woven bone formation was a characteristic feature and was related to the severity of osteitis fibrosa. There were significant correlations between the weights of parathyroid glands and the number of osteoclasts, amounts of woven bone, and marrow fibrosis in the ilium. Hyperparathyroidism caused degradation of mineralized bone but the loss was balanced or exceeded by the aggradation of woven mineralized bone. Woven bone formation together with excess osteoid gave rise to osteosclerosis. The histological findings indicate that hyperparathyroidism and osteitis fibrosa usually occur early in chronic renal failure and that osteomalacia develops subsequently.Chronic renal failure may be accompanied by bone disease (Stanbury, 1957(Stanbury, , 1972 and the changes, which include osteitis fibrosa due to secondary hyperparathyroidism, osteomalacia and osteosclerosis, may conveniently be termed renal osteodystrophy (Liu and Chu, 1943). Although it is recognized that the clinical effects of such changes may be severe in childhood (Claireaux, 1953;Haust, Landing, Holmstrand, Currarino, and Smith, 1964) 20 December 1972. in this study it appeared that there were histological differences between the bone changes in dialysed and non-dialysed patients. The latter tended to show osteitis fibrosa, osteomalacia, and a normal or raised total bone mass with normal or elevated amounts of mineralized bone. In contrast, in the bones of dialysed patients there was a loss of mineralized lamellar bone and total bone after about one or two years on dialysis. In others, following more prolonged dialysis, the total bone mass was elevated due to excess osteoid formation whilst the amount of mineralized bone remained low. The bones of dialysed patients in general also showed less severe changes of osteitis fibrosa (Ellis and Peart, 1971).To determine whether or not these differences were real it became necessary to quantitate the amounts of mineralized bone and osteoid present and the severity of the osteitis fibrosa. Critical quantitative histological studies of the mineralized and non-mineralized bone in renal failure were lacking until Garner and Ball (1966) reported their findings in 42 controls and in 18 selected cases of azotaemic renal osteodystrophy using a pointcounting technique to study undecalcified sections of iliac crest. As a basis for our quantitative observations in renal failure we have similarly studied the 83

SYNOPSISThe amounts of mineralized bone and osteoid in thin undecalcified sections of iliac crest have been measured in 68 control subjects at necropsy using a point-counting method. The effect of varying the site selected for quantitative study on the value obtained for total bone mass has been investigated in decalcified sections of iliac crest.The total bone mass shows individual variation within a fairly constant range with a mean of 22'7 ± 0 5% up to the age of 50 years and then progressively falls to a mean of 15-5 ± 11% for individuals aged > 50 years. Some of the lowest values in the range 5-5 to 16-4 (mean 8-9 ± 1-9 %) were observed in elderly women in the seventh to ninth decades. It is concluded that so-called senile osteoporosis is usually a manifestation of a normal aging process. In controls osteoid accounts for only about 0-1 % of the area measured and for a maximum of 1-8 % of bone with a mean mineralization of 99-5 %. Osteoid is patchily distributed and the maximum number of birefringent lamellae in any seam is four.The results of quantitative histology carried out in different parts of the iliac crest indicate that there are variations with the distance of the site from the anterior superior spine and its depth below the crest surface. The importance of this in relation to the site and size of iliac crest biopsies used for quantitative histology is discussed.There is a significant correlation between the values for total bone mass when estimated by the point-counting technique in undecalcified sections and by a volumetric method using blocks of bone.

This paper explores in patients with dialysis osteodystrophy the relationship between clinical features and histological, radiological, and biochemical findings. Eighty-five patients treated by hemodialysis for more than 6 months were studied. The following conclusions were drawn: 1) Bone pain in patients on regular hemodialysis is usually a symptom of developing osteomalacia but not of hyperparathyroidism or osteoporosis. 2) Many patients with histological osteomalacia and radiological features of osteomalacia, such as fractures or Looser zones, have no symptoms. 3)In dialysis patients, biochemical and radiological abnormalities are not a reliable means of predicting the presence of osteomalacia, but a raised serum alkaline phosphatase is a good indicator of the presence of osteitis fibrosa. For early detection of osteomalacia, bone biopsy in necessary. 4)A number of our dialysis patients develop an unusual form of osteomalacia characterized by absent or minimal histological osteitis fibrosa, a normal serum alkaline phosphatase, and a high incidence of myopathy and fractures.

In a previous paper we reported that there is an increase in the number of marrow mast cells in the iliac bone marrow of patients with chronic renal failure. Although mast cells occur in the marrow fibrous tissue associated with osteitis fibrosa, this is not the sole cause of the increase, since there is also an excess of mast cells in the non-fibrous marrow. We were unable to relate the number of mast cells to the presence or the severity of osteomalacia. The patients were in or near end-stage renal failure and although some had been treated by short-term peritoneal dialysis or by terminal haemodialysis none was on regular haemodialysis.In the present paper we describe the results of observations on the numbers of iliac bone marrow mast cells in patients being treated by haemodialysis with parallel observations on the severity of osteitis fibrosa and osteomalacia, which are the two main histological abnormalities in azotaemic renal osteodystrophy (Ellis and Peart, 1973). We also report the results of serial observations on marrowmast cell numbers in patients treated by oral aluminium hydroxide or by parathyroidectomy to relieve hyper-

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