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HYPOPHOSPHATAEMIC OSTEOMALACIA IN ADULTS
1343
the development of renal failure after injury. It can often be prevented, he suggests, by adequate replacement of blood-loss, and has become an unusual complication in his hospital, where this policy of replacement is energetically pursued. Some cases are still seen after abdominal injuries, when vomiting, dehydration, and electrolyte imbalance are presumably
concerned; and others
are
precipitated by major pul-
monary embolism. For none is any specific therapy available. There are some institutions abroad (such as the Central Institute of Traumatology in Budapest) which,
though specialising in accident surgery, have wholetime physicians on their staff. Even the biggest such hospital in this country calls only on a part-time Sevitt argues that the creation of new medical consultant posts in this area is now due.
physician as necessary.
other features of previous rickets. The age-range of onset was 14-41 years (average 28 years); and the male/female ratio was 2/1. All known causes of secondary vitamin-D-resistant osteomalacia were excluded and there was no evidence of rarer associated conditions, such as neurofibromatosis, Wilson’s disease, hypercalciuria, toxic states, or any of the various forms of adult-presenting Fanconi syndrome with aminoaciduria.2 All the reported cases have been sporadic and the family history has been completely negative. The syndrome usually presents as a combination of bone pain, muscle weakness, and often considerable loss of height (shortening of the upper segment, crown to pubis, due to vertebral collapse). Myopathy is present in all patients, and in this respect the syndrome resembles the osteomalacia of simple vitamin-D lack6 and contrasts with sex-linked vitaminD-resistant rickets in which muscle weakness is not a
feature. HYPOPHOSPHATAEMIC OSTEOMALACIA IN ADULTS
SINCE the early descriptions of vitamin-D-resistant rickets1 many distinct clinical and biochemical varieties of the disease have been defined.2 Resistance to vitamin D arises not only as a primary disorder but also as a disturbance secondary to such conditions as chronic renal failure and steatorrhoea. The term has been primary hypophosphataemia preferred in order to distinguish that broad group of patients with rickets and osteomalacia in which permanent hypophosphatsemia results from the excessive renal tubular loss of phosphate, considered to be the fundamental or primary biochemical abnormality. This abnormality is usually of genetic origin. Some evidence exists to indicate that patients with primary hypophosphataemia have an associated, or possibly primary, defect in intestinal phosphate transport.3A tubular abnormality of phosphate handling may be isolated or may coexist with additional renal tubular transport disorders. When multiple defects of renal tubular function exist, involving the reabsorption of phosphate, potassium, glucose, aminoacids, and water, the syndromes are usually named after De Toni, Debre, and Fanconi.4 The diagnosis of primary hypophosphataemia poses the least difficulty when it presents as vitamin-Dresistant rickets in early childhood, usually with a family history compatible with sex-linked dominant transmission. Multiple bone deformities are features of this syndrome, which may remit spontaneously in late adolescence or early adult life. In some patients pregnancy and lactation may cause symptoms to reappear, or they may present with osteomalacia in later adult life. But these affected h3Tophosphatxmic adults will always show signs of childhood rickets. Dent and Stamp 5 give details of 9 patients of their own and review 10 earlier cases with the syndrome of primary hypophosphataemic osteomalacia presenting for the first time after childhood without dwarfism or 1. 2. 3. 4.
Albright, F., Butler, 1937, 54, 529.
A.
M., Bloomberg,
E. Am.
J. Dis. Child.
Dent, C. E. Proc. R. Soc. Med. 1970, 63, 401. Condon, J. R., Nassim, J. R., Rutter, A. Br. med.J. 1970, iii, 138. Fourman, P., Royer, P. in Calcium Metabolism and the Bone; p. 444. Oxford, 1968. 5. Dent, C. E., Stamp, T. C. B. Q.Jl Med. 1971, 40, 303.
The radiological and biochemical findings in this syndrome are comparable with those in the sex-linked form of vitamin-D-resistant rickets and osteomalacia. Plasma-calcium concentrations are normal, sometimes near the upper limits, with low normal urine-calcium excretion. Plasma-alkaline-phosphatase activity is usually raised, although the increase is not as striking as would be expected from the severity of the bone disease. The hypophosphataemia is associated with a high renal phosphate clearance, and Dent and Stamp believe that this is the fundamental biochemical abnormality of adult-presenting primary osteomalacia. In 7 of their 9 patients they studied the renal tubular handling of phosphate by measuring the theoretical renal phosphorus threshold.’7 In all 7 this threshold was below the lower limit of the normal range, and no consistent change was seen at any stage of treatment with vitamin D either alone or with phosphate supplements. In two-thirds of Dent and Stamp’s patients there was also an isolated renal tubular leak of glycine; although the possible setiological significance of this was not clear, they believe that it should be regarded as a further characteristic of the
syndrome. Treatment requires oral phosphate supplements, probably for life, in addition to high doses of vitamin D. Calcium balances in the untreated state were either moderately negative or virtually zero in some patients who had received earlier treatment with vitamin D. On treatment with large doses of vitamin D alone, there was an increase in the previously low urine calcium excretion which nearly offset the fall in fascal excretion to produce small positive balances. Treatment with oral phosphate supplements alone was alsoassociated with small positive calcium balances and a. fall in urine-calcium excretion. Striking improvements in calcium balance occurred, however, when phosphate supplements were added to high doses of vitamin D, and the calcium intake then became the factor limiting the degree of positive balance during the healing phase. The early stages of treatment with a regimen of vitamin D, phosphate, and calcium were often associated with an increase in bone pain, accompanied by a temporary rise in plasma-alkaline-phosphatase activityn 6. 7.
Smith, R., Stern, G. J. neurol. Sci. 1969, 8, 511. Stamp, T. C. B., Stacey, T. E. Clin. Sci. 1970, 39, 505.
the development of renal failure after injury. It can often be prevented, he suggests, by adequate replacement of blood-loss, and has become an unusual complication in his hospital, where this policy of replacement is energetically pursued. Some cases are still seen after abdominal injuries, when vomiting, dehydration, and electrolyte imbalance are presumably
concerned; and others
are
precipitated by major pul-
monary embolism. For none is any specific therapy available. There are some institutions abroad (such as the Central Institute of Traumatology in Budapest) which,
though specialising in accident surgery, have wholetime physicians on their staff. Even the biggest such hospital in this country calls only on a part-time Sevitt argues that the creation of new medical consultant posts in this area is now due.
physician as necessary.
other features of previous rickets. The age-range of onset was 14-41 years (average 28 years); and the male/female ratio was 2/1. All known causes of secondary vitamin-D-resistant osteomalacia were excluded and there was no evidence of rarer associated conditions, such as neurofibromatosis, Wilson’s disease, hypercalciuria, toxic states, or any of the various forms of adult-presenting Fanconi syndrome with aminoaciduria.2 All the reported cases have been sporadic and the family history has been completely negative. The syndrome usually presents as a combination of bone pain, muscle weakness, and often considerable loss of height (shortening of the upper segment, crown to pubis, due to vertebral collapse). Myopathy is present in all patients, and in this respect the syndrome resembles the osteomalacia of simple vitamin-D lack6 and contrasts with sex-linked vitaminD-resistant rickets in which muscle weakness is not a
feature. HYPOPHOSPHATAEMIC OSTEOMALACIA IN ADULTS
SINCE the early descriptions of vitamin-D-resistant rickets1 many distinct clinical and biochemical varieties of the disease have been defined.2 Resistance to vitamin D arises not only as a primary disorder but also as a disturbance secondary to such conditions as chronic renal failure and steatorrhoea. The term has been primary hypophosphataemia preferred in order to distinguish that broad group of patients with rickets and osteomalacia in which permanent hypophosphatsemia results from the excessive renal tubular loss of phosphate, considered to be the fundamental or primary biochemical abnormality. This abnormality is usually of genetic origin. Some evidence exists to indicate that patients with primary hypophosphataemia have an associated, or possibly primary, defect in intestinal phosphate transport.3A tubular abnormality of phosphate handling may be isolated or may coexist with additional renal tubular transport disorders. When multiple defects of renal tubular function exist, involving the reabsorption of phosphate, potassium, glucose, aminoacids, and water, the syndromes are usually named after De Toni, Debre, and Fanconi.4 The diagnosis of primary hypophosphataemia poses the least difficulty when it presents as vitamin-Dresistant rickets in early childhood, usually with a family history compatible with sex-linked dominant transmission. Multiple bone deformities are features of this syndrome, which may remit spontaneously in late adolescence or early adult life. In some patients pregnancy and lactation may cause symptoms to reappear, or they may present with osteomalacia in later adult life. But these affected h3Tophosphatxmic adults will always show signs of childhood rickets. Dent and Stamp 5 give details of 9 patients of their own and review 10 earlier cases with the syndrome of primary hypophosphataemic osteomalacia presenting for the first time after childhood without dwarfism or 1. 2. 3. 4.
Albright, F., Butler, 1937, 54, 529.
A.
M., Bloomberg,
E. Am.
J. Dis. Child.
Dent, C. E. Proc. R. Soc. Med. 1970, 63, 401. Condon, J. R., Nassim, J. R., Rutter, A. Br. med.J. 1970, iii, 138. Fourman, P., Royer, P. in Calcium Metabolism and the Bone; p. 444. Oxford, 1968. 5. Dent, C. E., Stamp, T. C. B. Q.Jl Med. 1971, 40, 303.
The radiological and biochemical findings in this syndrome are comparable with those in the sex-linked form of vitamin-D-resistant rickets and osteomalacia. Plasma-calcium concentrations are normal, sometimes near the upper limits, with low normal urine-calcium excretion. Plasma-alkaline-phosphatase activity is usually raised, although the increase is not as striking as would be expected from the severity of the bone disease. The hypophosphataemia is associated with a high renal phosphate clearance, and Dent and Stamp believe that this is the fundamental biochemical abnormality of adult-presenting primary osteomalacia. In 7 of their 9 patients they studied the renal tubular handling of phosphate by measuring the theoretical renal phosphorus threshold.’7 In all 7 this threshold was below the lower limit of the normal range, and no consistent change was seen at any stage of treatment with vitamin D either alone or with phosphate supplements. In two-thirds of Dent and Stamp’s patients there was also an isolated renal tubular leak of glycine; although the possible setiological significance of this was not clear, they believe that it should be regarded as a further characteristic of the
syndrome. Treatment requires oral phosphate supplements, probably for life, in addition to high doses of vitamin D. Calcium balances in the untreated state were either moderately negative or virtually zero in some patients who had received earlier treatment with vitamin D. On treatment with large doses of vitamin D alone, there was an increase in the previously low urine calcium excretion which nearly offset the fall in fascal excretion to produce small positive balances. Treatment with oral phosphate supplements alone was alsoassociated with small positive calcium balances and a. fall in urine-calcium excretion. Striking improvements in calcium balance occurred, however, when phosphate supplements were added to high doses of vitamin D, and the calcium intake then became the factor limiting the degree of positive balance during the healing phase. The early stages of treatment with a regimen of vitamin D, phosphate, and calcium were often associated with an increase in bone pain, accompanied by a temporary rise in plasma-alkaline-phosphatase activityn 6. 7.
Smith, R., Stern, G. J. neurol. Sci. 1969, 8, 511. Stamp, T. C. B., Stacey, T. E. Clin. Sci. 1970, 39, 505.