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PubMed2004

Infrared imaging of calcified tissue in bone biopsies from adults with osteomalacia.

Osteomalacia is a pathological bone condition in which there is deficient primary mineralization of the matrix, leading to an accumulation of osteoid tissue and reduced bone mechanical strength. The hypothesis that there are no qualitative or quantitative differences in osteomalacic bone mineral or matrix compared to disease-free bones was tested by examining unstained sections of polymethyl methacrylate (PMMA) embedded iliac crest biopsies using Fourier transform infrared imaging (FTIRI) at approximately 6-microm spatial resolution. Controls were seven female subjects, aged 36-57, without apparent bone disease. The experimental group consisted of 11 patients aged 22-72, diagnosed with osteomalacia. The spectroscopic parameters analyzed in each data set were previously established as sensitive to bone quality: phosphate/amide I band area ratio (mineral content), 1660/1690 cm(-1) peak ratio (collagen cross-links), and the 1030/1020 cm(-1) peak ratio (mineral crystallinity). The correspondence between spectroscopic mineral content (phosphate/amide I ratio) and ash weight was validated for apatite crystals of different composition and crystallite size. The FTIRI results from the biopsies expressed as color-coded images and pixel population means were compared with the nonparametric Mann-Whitney U test. There were no significant differences in the cortical parameters. Significant difference was found in the mineral content of the trabecular regions with a lower mean value in osteomalacia (P = 0.01) than in controls. Mineral crystallinity tended to be decreased in the trabecular bone (P = 0.09). This study supports the hypothesis that, in osteomalacia, the quality of the organic matrix and of mineral in the center of bone does not change, while less-than-optimal mineralization occurs at the bone surface. This study provides the first spectroscopic evaluation of whole bone mineral and matrix properties in osteomalacia, demonstrating that there are few differences in collagen cross-links between biopsies from patients with osteomalacia and from individuals without histological evidence of bone disease.

Adult↗

PubMed1995

Tumor-induced osteomalacia.

Tumor-induced (oncogenic) osteomalacia is a rare clinicopathologic entity in which the clinical signs and symptoms of osteomalacia and the specific laboratory abnormalities of hypophosphatemia, hyperphosphaturia, and low serum levels of 1,25(OH)2 vitamin D are associated with the finding of a neoplastic process in the patient. To date, less than 100 cases of oncogenic osteomalacia have been described. We report a new case of adult-onset hypophosphatemic osteomalacia leading to the discovery of an asymptomatic phosphaturic mesenchymal lung tumor. Complete resection of the pulmonary neoplasia was followed by rapid normalization of the laboratory findings and clinical remission. The clinical, laboratory, and histopathologic spectrum of tumor-induced osteomalacia is presented, and the postulated mechanism of this condition is discussed in light of the relevant literature. The presence of occult neoplasms should be considered in cases of unexplained adult osteomalacia, with the physician's efforts being rewarded by the dramatic cure that follows excision of the tumor.

Adult↗

PubMed1997

Osteomalacia.

Osteomalacia is a generalized bone disorder characterized by impairment of mineralization, leading to accumulation of unmineralized matrix or osteoid in the skeleton. The classical clinical features of osteomalacia include musculoskeletal pain, skeletal deformity, muscle weakness and symptomatic hypocalcaemia. In childhood the features of osteomalacia are accompanied by rickets, with widening of the epiphyses and impaired skeletal growth. The major cause of osteomalacia is vitamin D deficiency, which is most often due to reduced cutaneous production of vitamin D in housebound elderly people, immigrants to Northern countries and women who adopt strict dress codes which prohibit exposure of uncovered skin. Vitamin D deficiency osteomalacia may also occur with malabsorption, liver disease and anticonvulsant therapy. Less commonly, osteomalacia may result from abnormal vitamin D metabolism, resistance to the action of vitamin D, hypophosphataemia or toxic effects on osteoblast function.

Calcium↗

PubMed2003

Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.

BACKGROUND: Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic rickets. Clinical and laboratory findings in this disorder are similar to those in oncogenic osteomalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosphatemia, which is caused by inactivating mutations in a phosphate-regulating endopeptidase called PHEX. Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo, suggesting that it has a role in phosphate regulation. To determine whether FGF-23 circulates in healthy persons and whether it is elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, an immunometric assay was developed to measure it. METHODS: Using affinity-purified, polyclonal antibodies against [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, we developed a two-site enzyme-linked immunosorbent assay that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substituted for arginine at position 179 (R179Q), and synthetic human FGF-23(207-244)amide. Plasma or serum samples from 147 healthy adults (mean [+/-SD] age, 48.4+/-19.6 years) and 26 healthy children (mean age, 10.9+/-5.5 years) and from 17 patients with oncogenic osteomalacia (mean age, 43.0+/-13.3 years) and 21 patients with X-linked hypophosphatemia (mean age, 34.9+/-17.2 years) were studied. RESULTS: Mean FGF-23 concentrations in the healthy adults and children were 55+/-50 and 69+/-36 reference units (RU) per milliliter, respectively. Four patients with oncogenic osteomalacia had concentrations ranging from 426 to 7970 RU per milliliter, which normalized after tumor resection. FGF-23 concentrations were 481+/-528 RU per milliliter in those with suspected oncogenic osteomalacia and 353+/-510 RU per milliliter (range, 31 to 2335) in those with X-linked hypophosphatemia. CONCLUSIONS: FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, suggesting that this growth factor has a role in phosphate homeostasis. FGF-23 measurements might improve the management of phosphate-wasting disorders.

Adolescent↗

PubMed1994

Tumor-induced osteomalacia.

Tumor-induced or oncogenous osteomalacia is a rare paraneoplastic syndrome characterized by osteomalacia with hypophosphatemia, hyperphosphaturia, and undetectable or inappropriately low circulating concentrations of 1,25-dihydroxyvitamin D3. The syndrome is associated with the presence of a tumor whose successful removal leads to clinical and biochemical cure. More than 80 cases of tumor-induced osteomalacia have been reported, but recognition of affected persons is still frequently delayed or neglected. This has been due, in part, to difficulty in locating the tumors that cause the disorder, but it may also be the result of inappropriate assessment of the cause of hypophosphatemia. Progress in identifying the pathophysiology of tumor-related osteomalacia has therefore been limited. However, there may be homologies between tumor-related osteomalacia and inherited hypophosphatemia. Studies of the latter, which are included in this review, may help to elucidate the factor or factors that cause tumor-induced osteomalacia.

Adult↗

PubMed2005

Histological evaluation of biopsies obtained from vertebral compression fractures: unsuspected myeloma and osteomalacia.

STUDY DESIGN: A histological evaluation of biopsies obtained from presumed osteoporotic vertebral compression fractures (VCF) to confirm possible osteomalacia after tetracycline labeling. OBJECTIVE: To describe the results of a series of biopsies obtained at the time of vertebral augmentation in presumed osteoporotic VCF, with special reference to the presence of unmineralized bone (osteomalacia) and occult or unconfirmed plasma cell dyscrasia. SUMMARY OF BACKGROUND DATA: Vertebral augmentation is now widely performed as a method to treat osteoporotic or osteolytic VCF. However, the influence of underlying pathology on the effect of treatment is unclear. METHODS: As of October 2003, 178 biopsies were obtained from 142 patients with VCF during 246 kyphoplasty procedures. There were 110 one-level, 28 two-level, and 4 three-level biopsies. Patients included 41 men and 101 women, with an average age of 72 years (range 40-90). The patients consented to this procedure, and 25 received tetracycline (1g/day, in 2 doses separated by 6 days). Vertebral body biopsies were taken using a trephine just before the kyphoplasty procedure. The biopsies were fixed, embedded, and stained with toluidine blue and hematoxylin eosin, and were viewed with transmitted light. Unstained sections were viewed under fluorescent light to detect tetracycline labels. RESULTS: The 178 biopsy levels included: T4 (3), T5 (1), T6 (4), T7 (13), T8 (12), T9 (8), T10 (11), T11 (17), T12 (28), L1 (25), L2 (14), L3 (13), L4 (17), and L5 (12). All specimens showed fragmented bone with variable amounts of unmineralized bone (osteoid), suggesting bone remodeling and/or fracture healing. Woven bone and cartilaginous tissue were often present, representing fracture callus formation. The biopsies obtained from 30 patients (21%), including 4 who received tetracycline, showed significantly increased osteoid, suggesting either increased bone remodeling activity or mineralization defect (osteomalacia). One sample from these 4 patients who received tetracycline showed no tetracycline labels, essentially diagnostic of osteomalacia. The biopsies also provided definitive diagnoses for one case of unsuspected and 3 cases of unconfirmed plasma cell dyscrasia. CONCLUSIONS: The majority of biopsies from this series of patients revealed findings consistent with various stages of fracture healing. Osteoid seams were increased in 30 patients, representing either increased bone remodeling or osteomalacia. More cases with tetracycline labeling will help elucidate the true incidence of osteomalacia in this population. As we confirmed 4 cases of plasma cell dyscrasia, we advocate a biopsy during each first-time vertebral augmentation procedure.

Adult↗

PubMed1992

Histological and electron microprobe studies of mineralisation in aluminium-related osteomalacia.

AIMS: To determine a possible mechanism to explain the presence of aluminium lines within fully calcified bone in aluminium-related osteomalacia. METHODS: Fifty five bone cases shown by bone biopsy to be aluminium-related osteomalacia were studied. In 38 specimens aluminium lines were identified within calcified bone by means of the Aluminon stain and a characteristic form of patchy mineralisation was seen within thickened osteoid seams. Five representative examples were analysed quantitatively by histomorphometry and electronprobe X-ray microanalysis and compared with five cases of vitamin D deficiency-related osteomalacia which also had patchy mineralisation. RESULTS: The patchy calcification occupied 40 +/- 8% (mean +/- SEM) of the osteoid and consisted of small focal deposits (less than 40 microns diameter), often (52%) around osteoid osteocytes (probably an underestimate of the association), and larger areas that extended to the aluminium lines at the underlying mineralisation front. Small and large mineralisation nuclei were seen ultrastructurally in the patchy calcification. Quantitative electronprobe X-ray microanalysis showed that calcium concentrations and calcium:phosphorus ratios in the mineralisation nuclei and in the superficial layer of the fully calcified bone of the aluminium-related osteomalacia cases were significantly less than values measured at similar sites in the vitamin D deficiency-related osteomalacia cases. Furthermore, aluminium could not be detected by means of this technique at the mineralisation front or along cement lines in these specimens. CONCLUSIONS: Calcification can occur in thickened osteoid seams in osteomalacia. It can begin around osteoid osteocytes as small deposits that enlarge within the osteoid and extend to the underlying mineralisation front or cement line where aluminium lines may become trapped. Complete calcification of osteoid could account for the presence of aluminium lines within fully calcified bone. The Aluminon stain appears to be a more sensitive method for the detection of aluminium in bone than electronprobe X-ray microanalysis.

Adult↗

PubMed1987

Osteomalacia and aplastic bone disease in aluminum-related osteodystrophy.

The bone histology in patients with chronic renal failure and aluminum-related bone disease does not always show the excess accumulation of unmineralized osteoid (matrix) characteristic of osteomalacia. Frequently, bone aluminum accumulation is associated with normal or reduced amounts of unmineralized osteoid and low bone formation and is referred to as aplastic bone disease. In this study, we compared static and dynamic bone histomorphometric parameters and plasma PTH and aluminum levels in 12 patients with osteomalacia and 18 patients with aplastic bone disease who had been receiving dialysis for the same duration to determine if the difference in osteoid accumulation in these 2 lesions might be explained by differences in aluminum accumulation or PTH levels. The stainable bone surface aluminum level was significantly higher in the patients with osteomalacia compared to that in the group with aplastic bone [61 +/- 5% (+/- SEM) vs. 43 +/- 4%; P less than 0.02]. The rates of bone apposition and bone formation were lower in the group with osteomalacia (P less than 0.01). Plasma amino-terminal PTH was not significantly different in the 2 groups. The increment in plasma aluminum levels after a single infusion of deferoxamine was higher in the osteomalacic group than in the aplastic group, suggesting that the patients with osteomalacia accumulated more total body chelatable aluminum than did those with aplastic bone disease during a comparable length of time on dialysis. We conclude that the excess unmineralized osteoid in aluminum-related osteomalacia results from the high rate of total body aluminum accumulation, which directly causes uncoupling of matrix mineralization and matrix production, independent of PTH levels. Patients with aplastic bone disease who have accumulated lesser amounts of total body aluminum fail to develop excess unmineralized osteoid because production and mineralization of matrix are more closely coupled than in the osteomalacic lesion, despite a decline in osteoblast numbers.

Adult↗

PubMed2005

Osteomalacia in Hazara District, Pakistan.

Osteomalacia is most commonly seen in the remoter northern regions (Kohistan District) of Hazara District, Pakistan. Low serum calcium is common, as is tetany, but not universal. A 2% prevalence was found retrospectively in all obstetric patients from 1978--1985. Overall, there was a 12% caesarean section rate (61/annum), of which 37% (22) exhibited cranio-pelvic disproportion, nearly half of which (n=83, 46%) were thought clinically to be due to osteomalacia. Osteomalacia was found prospectively in 3.6% of all female outpatients (3600/100,000). Purdah did not appear to influence the incidence of osteomalacia, although sunlight exposure varied significantly due to place of abode (0.05 > P> 0.025); those living in the deeper, darker valleys suffered more from osteomalacia and its side effects, such as cranio-pelvic disproportion and the resulting need for caesarean sections. Diet is an important factor, showing little variety in the affected region; it lacks animal protein and is low in calories.The estimated intake of vitamin D is approximately 1 microg per day, seriously short of the daily requirement of 2.5 microg. The other main factor is higher parity in the women with osteomalacia (15/18 affected women had more than three pregnancies compared with 9/18 controls; odds ratio 13, 0.05 > P> 0.025). These all indicate that in a marginal situation added metabolic stress can precipitate the condition. While supplementation of the diet is essential in such communities it will be difficult to initiate and maintain. We therefore also recommend that strategies for prevention be focused on the men to encourage them to help improve the diet and lifestyle of their womenfolk.

Adult↗

PubMed1998

Saccharated ferric oxide-induced osteomalacia in Japan: iron-induced osteopathy due to nephropathy.

Saccharaed ferric oxide (SFO)-induced osteomalacia develops when excessive SFO infusions are administrated to patients with anemia for prolonged periods for a few years. The small particles and almost neutral saccharide of SFO filter through the glomerular tufts into the renal tubules, resulting in impairment of proximal renal tubular function, particularly renal reabsorption of phosphate and 1alpha-hydroxylase activity, resulting in decreased serum levels of phosphorus and active vitamin D, both of which lead to development of hypophosphatemic osteomalacia. Furthermore, SFO, at concentrations attainable in serum, exacerbates the osteomalacia by inhibiting bone formation directly. In contrast to itai-itai disease, another iatrogenic osteomalacia due to cadmium nephropathy [44], the proximal renal tubular function impairment induced by SFO is reversible simply by discontinuing the nephrotoxin, which is followed by improvement of all the clinical manifestations, except bone deformities. So far, SFO-induced osteomalacia, that is, SFO-induced osteopathy due to nephropathy, has been reported only in Japan, probably due to the lax surveillance system of the health insurance scheme. All physicians who prescribe SFO should be aware of its severe adverse effects. We hope that such iatrogenic osteomalacia caused by abusive infusion of SFO will never again be reported in our country.

Aged↗

PubMed1992

Clinical and histological spectrum of osteomalacia among Asians in south London.

In a prospective study of 175 adult Asian patients attending a medical out-patient clinic we found a spectrum of metabolic bone disease. Twenty-four patients (13.5 per cent) had definite osteomalacia, of whom 11 (6 per cent) had severe clinical osteomalacia on the basis of associated symptoms and radiological signs. Fifteen (8.5 per cent) had borderline osteomalacia, while the remaining 136 (78 per cent) had normal bone biopsy, or were presumed to be normal. This histological spectrum was paralleled by the increasing prevalence of musculoskeletal symptoms (thigh pain, change in gait and difficulty rising from seated position) attributable to osteomalacia. Multivariate analysis showed that the major determinant of osteomalacia in Asians in South London was vegetarian diet. Increasing severity of bone disease was associated with increasingly strict vegetarian practice, which accounted for the excess risk of females, Hindus, and Asians originating from East Africa. Covering skin when outdoors also contributed to the female excess risk, and suggested a role for reduced solar exposure. Clinically significant osteomalacia is underdiagnosed in the Asian population, but evidence of dietary adaptation suggests this problem may diminish with time.

Adult↗

PubMedDate not supplied

Is a certain degree of osteomalacia involved in femoral neck fractures of the elderly? Histological approach to the problem and practical applications.

A study was made in Geneva of 14 patients with femoral neck fractures (7 subcapital and 7 trochanteric) to determine whether a certain degree of osteomalacia might be involved (group I). No patients with risks factors for osteomalacia were used. For ethical reasons, double tetracycline labelling was not possible and osteomalacia criteria were based on osteoid tissue values determined in a histomorphometric study directly on cancellous bone samples of the femoral head. A comparison was made with femoral head bone tissue taken from 12 patients with hip osteoarthritis at a distance from the remodelled territory (group II) and with iliac crest bone tissue taken from 6 patients with clinically and biochemically determined osteomalacia (group III). The patients were part of a larger group of subjects used for a biochemical blood study in which levels of albumin, calcium and 25 OHD3 as an index of vitamin D content were determined. Based on the data of the literature and the results obtained for group II, slight signs of osteomalacia were diagnosed for only one case (group I), although 25 OHD3 deficiency was found in more than a third of the subjects in that group as well as in some subjects of group II and in some of the aged controls. Skeletal aging must be considered not only in terms of unavoidable physiological factors but also within the context of living conditions. Hence the necessity of controlling calcium and vitamin D intake in the elderly, and of a histological examination for signs of osteomalacia in surgical specimens from patients with femoral neck fractures.

Aged↗

PubMed1982

Osteomalacia, vitamin D deficiency and cholestasis in chronic liver disease.

Twenty-nine patients with chronic liver disease, nine of whom had symptoms suggesting bone disease, were studied by bone histology. Nine had osteomalacia; six associated with cholestatic liver disease and three with primarily hepatocellular disease. Two of these had clinical and biochemical features of cholestasis for at least a year and the other had alcoholic cirrhosis associated with severe malnutrition. Excluding the latter patient, histological osteomalacia was significantly associated with presence and duration of cholestasis. Plasma 25-hydroxyvitamin D was low and fasting urine hydroxyproline/creatinine ratio was high in all patients with osteomalacia but were abnormal also in some patients who did not have histological osteomalacia. Serum calcium, phosphate, alkaline phosphatase, vitamin D-binding protein and radiology were unhelpful in many patients with osteomalacia. Vitamin D-deficiency correlated significantly with deficiency of other fat-soluble vitamins and those patients with rachitic levels of plasma 25-hydroxyvitamin D showed no seasonal variation, suggesting a combination of malabsorption of vitamin D and reduced sunlight exposure. We suggest that patients with chronic liver disease with cholestasis for at least a year are at risk from osteomalacia and that those likely to have this complication may be identified by plasma 25-hydroxyvitamin D and/or fasting urine hydroxyproline/creatinine ratio measurements. The diagnosis can only be made with certainty by bone biopsy.

25-Hydroxyvitamin D 2↗

PubMed2003

Oncogenic hypophosphatemic osteomalacia associated with a nasal hemangiopericytoma.

We report a patient with a nasal hemangiopericytoma associated with an oncogenic hypophosphatemic osteomalacia (OHO). This syndrome results from tumor products that decrease renal tubular phosphate resorption, leading to the osteomalacia. This patient presented with classic bone manifestations of osteomalacia and a nasal tumor. Laboratory studies performed before the first resection of the tumor included normal serum calcium, hypophosphatemia due to decreased tubular reabsorption of phosphate, and an undetectable serum 1,25 dihydroxy vitamin D level. Serum parathormone level was normal. Anterior iliac crest bone biopsy showed characteristic signs of osteomalacia that included increased osteoid and delayed mineralization. A partial resection of the nasal tumor was performed. After the first surgery the patient showed detectable serum level of 1,25 dihydroxy vitamin D, and transient normalization of the tubular reabsorption of phosphate. The patient was also treated with phosphate supplements and vitamin D with transient control of her clinical manifestations and improvement of the radiographic signs of osteomalacia. Three months after surgery, the serum level of 1,25 dihydroxy vitamin D level again became undetectable. After selective embolization of the tumor, followed by an apparent complete tumor resection and postoperative radiation therapy, her hypophosphatemia and decreased phosphate tubular reabsorption persisted. Therefore, biochemical changes associated with hemangiopericytoma induced OHO may persist even after apparent total tumor resection. Clinicians should be aware of the oncogenic basis for some osteomalacia, as seen in this patient.

Journal Article↗

PubMed1976

Calcium balance in drug-induced osteomalacia: response to vitamin D.

The effect of oral vitamin D3 therapy on calcium balance was compared in 18 institutionalized subjects with drug-induced osteomalacia and in 18 similar subjects without osteomalacia. The subjects with osteomalacia were receiving standard doses of phenytoin and phenobarbital. Diagnosis of osteomalacia was based on low serum calcium and phosphorus, elevated alkaline phosphatase, and appropriate roentgenographic bone changes. The study group achieved positive calcium balance at approximately 975 IU of vitamin D3 per day, while the control group achieved positive calcium balance at approximately 380 IU of vitamin D3 per day. The difference is highly significant (p less than 0.001). These data support previous observations that the osteomalacia of patients receiving anticonvulsant drugs is related to the drugs and that these patients require supplemental doses of vitamin D.

Adolescent↗

PubMed1990

Hypercalcemic hyperparathyroidism and hypophosphatemic osteomalacia complicating neurofibromatosis.

Neurofibromatosis is sometimes complicated by impaired renal tubular reabsorption of phosphate, hypophosphatemia, and osteomalacia. Hyperparathyroidism has also been reported in patients with neurofibromatosis. When hypercalcemia and elevated levels of parathyroid hormone are found in osteomalacia, however, it may be difficult to determine if the hyperparathyroidism was primary or tertiary. We describe a patient with neurofibromatosis, hypercalcemic hyperparathyroidism, hypophosphatemic osteomalacia, vitamin D deficiency, and clear-cell hyperplasia of all four parathyroid glands. Serial biomechanical, bone biopsy, and densitometric studies confirmed that treatment with ergocalciferol, calcium, and phosphate supplements significantly improved the osteomalacia but caused increased parathyroid overactivity. After subtotal parathyroidectomy, the parathyroid hormone concentration became normal and the bone mineral content increased at the spine and hip, but inappropriate phosphaturia persisted. The findings indicate that hyperparathyroidism, osteomalacia, and vitamin D deficiency adversely affect each other.

Bone and Bones↗

PubMed2007

Tumor-induced osteomalacia.

Tumor-induced osteomalacia, also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome in which vitamin D resistant osteomalacia occurs due to the presence of a tumor. The following case report describes a young woman who seeks a second opinion from a rheumatologist and is found to have oncogenic osteomalacia. Not often discussed in the rheumatology literature, oncogenic osteomalacia is a rare and interesting disease entity in which diagnosis is often more challenging than treatment.

Adult↗

PubMed1981

Axial osteomalacia. Clinical, laboratory and genetic investigation of an affected mother and son.

Axial osteomalacia--a rare osteosclerotic bone disorder characterized by axial skeleton pain, coarsening of the trabecular bone pattern on radiographs of the axial but not appendicular skeleton, and osteomalacia on biopsy of a rib or iliac crest--has been reported in 10 apparently sporadic cases, all of which were in middle-aged or elderly Caucasian men. The etiology is unknown but has been postulated to be a bone cell defect. We describe the clinical, laboratory, pathologic and family study of a black mother and son with axial osteomalacia associated with polycystic liver and kidney disease. Investigation of the son suggested that radiographic osteosclerosis can be detected in early adulthood. Limited skeletal survey of his three children revealed no abnormalities. Examination of undecalcified iliac crest bone after in vivo tetracycline labeling revealed severe osteomalacia in the son despite normal circulating calcium, inorganic phosphate and vitamin D metabolite levels and persistently elevated alkaline phosphatase activity. Although osteoblasts appeared flat and inactive, histochemical studies showed intense alkaline phosphatase activity in the osteoblasts along most trabecular bone surfaces. Electron microscopy revealed intact matrix vesicles within unmineralized osteoid. The presence also of unexplained myopathy in the son--characterized by proximal muscle weakness, persistently elevated circulating creatine phosphokinase levels and pathogenic changes of myopathy on biopsy of quadriceps muscle--together with impaired bone mineralization, suggests that a disorder of vitamin D action may be involved in the pathogenesis of this unusual condition. Axial osteomalacia affects blacks as well as Caucasians, women as well as men, may be familial, and may perhaps be a developmental abnormality inherited in association with polycystic kidney and liver disease.

Adolescent↗