- Email: [email protected]
Malignant hypophosphathaemic bone disease
European Journal of Radiology 37 (2001) 134– 138 www.elsevier.nl/locate/ejrad
Case report
Malignant hypophosphathaemic bone disease K. Kozlowski *, S. Posen Departments of Radiology Royal Alexandra Hospital for Children and Endocrinology, Metabolism Royal North Shore Hospital, Sydney, Australia Received 6 March 2000; received in revised form 13 June 2000; accepted 13 June 2000
Abstract A case of crippling osteoporosis with muscular weakness, hypophosphatemia, hyperparathyroidism, defective skeletal calcification and cartilage destruction is reported. The patient, a male was observed from the age of 212 until his death at the age of 33 years. This bone/cartilage disease failed to respond to phosphate supplementation, parathyroidectomy and calcitriol. We believe this may represent a hitherto undescribed entity. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Hypophosphathemia; Rickets; Osteoporosis; Hyperparathyroidism; Cartilage destruction
1. Introduction Hypophosphatemia is a common feature of different disorders presenting as rickets. We report a patient with hypophosphatemia, observed from the age of 212 until his death at the age of 33, who presented unique clinical course and distinctive radiographic features. To the best of our knowledge no similar disorder has yet been reported.
2. Case report This boy had been born to non-consanguinous, healthy parents after an uncomplicated pregnancy. His birth weight was 3.4 kg and his three siblings were normal. He passed the usual milestones up to the age of 15 months when he presented for the evaluation of progressive right knock-knee deformity and external rotation of the right foot. These features had been noted for the past 6 months. Radiological diagnosis at the time included ‘rickets’ and ‘Jansen’s metaphyseal dysplasia’. * Corresponding author. New Children’s Hospital, PO Box 3515 Parramatta, NSW 2124, Australia. Fax: +61-2-94382562.
The legs were kept in plaster for 2 months and then in calipes for a further 12 months. At the age of 212 years his height was 85 cm, and his weight 12.7 kg. From the age of 212 years he suffered from progressive difficulties with walking and it was noted that his growth rate was decreasing. At the age of 7 years he developed progressive weakness of the lower limbs and a neurologist expressed the opinion that there was ‘generalised muscle weakness’. Various neurological investigations performed at the time (pneumoencephalography, myelography, electromyography) revealed no abnormalities. By the age of 11 years his muscular weakness and wasting had become so severe that he had to use a wheelchair for distances greater than a few steps. A fall from the wheelchair at that time resulted in a fracture of the right femoral shaft. Physical examination at that stage showed normal face, short trunk, a ‘barrel chest’ deformity, a height of 121cm, a crown –pubis distance 58 cm, and a pubis –heel distance of 63 cm and a span of 136 cm. No abnormalities were detected in the lungs, the heart or the abdomen. His mental development was considered normal. During the remainder of his life, multiple examinations confirmed the presence of muscular weakness and hypotonia. The skeletal deformities showed a gradual progression (Fig. 1A–G). He also developed flexion
0720-048X/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 7 2 0 - 0 4 8 X ( 0 0 ) 0 0 2 4 7 - 3
K. Kozlowski, S. Posen / European Journal of Radiology 37 (2001) 134–138
135
Fig. 1. A, B: 212-year-old. Osteopenia. Radiolucent metaphyses with vertical trabecular pattern. Abnormal trabecular pattern of the epiphyses and diaphyses. C: 6-year-old. Osteopenia. The radiolucent areas moved away from the shaft. Flattened epiphyses. D: 10-year-old. Osteopenia. Platyspondyly. Flattening with posterior wedging of L2 vertebral body. E: 11-year-old. Osteopenia. Radiolucent metaphyses of the forearm bones. Dense punctate and linear calcification in the phalanges resemble a little bit ‘enchondromatosis’ and support the assumption that we are dealing with an uncomplete and disturbed differentiation of chondrocytes. Flattening of the distal forearm epiphyses. F, G: 13-year-old. Osteopenia. Radiolucent metaphyses. Flattened epiphyses. Irregular trabecular pattern with multiple small cyst-like radiolucences in the metaphyses, epiphyses and round bones. Narrow cortical bone.
136
K. Kozlowski, S. Posen / European Journal of Radiology 37 (2001) 134–138
deformities of the large joints and diffuse pain of increasing severity. The pain was aggravated by movement and relieved by rest. Multiple biochemical test over the years showed persistent hypophosphatemia with values ranging from 1.2 to 2.5 mg/dl (10.4 –0.8 mmol/l). Serum calcium, other serum electrolytes and serum alkaline phosphatase were normal during the first decade of life, as were all hematological investigations. At the age of 12 years he was subjected to metabolic balance studies in the laboratory of the late Dr C.E. Dent (London) who found negative calcium and phosphate balances (− 179 and − 97 mg/day, respectively) but no other abnormalities. At the age of 14 years he was hospitalised under the care of the late Dr L.V. Avioll (St. Louis) who performed multiple investigations including fecal fat estimations, a small bowel biopsy, Ca47 absorption studies and urine acidification tests. All of these gave normal results. Abnormal results at the time included glycinuria and elevated serum alkaline phosphatase (324 U) and serum PTH concentrations (11.1 ml Eq/ml — normal 2–8), initially in the presence of normocalcemia. Serum PTH elevation persisted and serum calcium concentrations were elevated some 12 years after the initial parathyroid investigations. Nephrogenous cyclic AMP was elevated (6.36 nmol/100 ml glomerular filtrate — normal less than 1.92) at the age of 26. Repeated iliac crest biopsies were interpreted by Dr S.L. Teitelbaum to show a combination of ‘osteomalacia and osteitis fibrosa’. Treatment included phosphate supplements, calcitriol and the removal of abnormally enlarged parathyroid glands (‘hyperplasia or adenoma’) at the age of 18 and again at the age of 28. None of these measures was of any apparent benefit. Calcitriol had to be discontinued on several occasions because of symptomatic hypercalcemia. He continued to suffer from pain and weakness so that during the last few years of his life he led a bed and wheelchair existence and required increasing quantities of narcotics. Biochemical tests at the age of 32 showed a serum PTH 200 pg/ml (norm 12 – 55), a serum calcium of 2.48 mmol/l (norm 2.25 – 2.65), a serum inorganic phosphate of 0.8 mmol/l (norm 0.8 – 1.15) and a serum alkaline phosphatase of 556 U/l (norm 30 – 115). The levels of serum 25-hydroxycalciferol and 1,25 dihydroxycalciferol were normal. He became increasingly dyspneic and died at the age of 38 years of suspected respiratory failure. Serial radiographic examinations from the age of 212 years to the age of 33 years showed progressive osteopenia with transradiant metaphyses and disorganised trabecular pattern in early childhood. Later the metaphyseal transradiancy moved into the shaft of the long bones and there was washing out of the trabecular pattern. Progressive narrowing of the joint spaces with
widening of the metaphyses was most marked in the big joints and in the carpus, where it simulated carpal fusion. In the spine platyspondyly and anisospondyly secondary to osteoporosis were seen in the first decade of life. In the second and third decades, documented were progressive compression deformity of the thoracic spine and lumbar spine varying between 50 and 75%, with kyphosis of the thoracic and hyperlordosis of the lumbar spine. The skull was severely demineralised with minor, later moderately severe platybasia. There was absence of lamina dura. In the pelvis progressive acetabular protrusion, deformity of the pelvic cavity, narrowing of the hip joint space, coxa vara and unusual popcorn pattern of the femoral heads were noted (Fig. 1A–G, and Fig. 2A –E). 3. Discussion This patient’s clinical and radiographic features do not correspond to any known disorder. The distinctive abnormalities included the combination of bony and cartilaginous changes, the early onset of the disease and the progressive course, which confined the patient to a wheelchair for 27 years. The clinical and radiological abnormalities were accompanied by persistent hypophosphatemia, at first in the absence of overt hyperparathyroidism but with clear evidence of hyperparathyroidism (hypercalcaemia, elevated serum PTH, elevated nephrogenous cyclic AMP, osteitis fibrosa, enlarged parathyroid glands) at the age of 26 years. However, the skeletal changes were quite unlike those of ‘parathyroid osteopathy’ [1–4]. The histological evidence for osteomalacia was also incontrovertible. Six different specimens of bone taken from the iliac crest over the period of 12 years all showed thick osteoid seams with ‘smeared’ fluorescent labels and a total absence of double labels. These findings were noted both on and off calcitriol therapy. However the osteopenic metaphyses and the large ‘empty’ areas in the shafts of the long bones were quite unlike the radiological signs of ‘rickets’, nor were the widened metaphyses, the popcorn appearance of the proximal femoral and humeral metaphyses and marked loss of joint cartilage characteristic of ‘osteomalacia’ [5–8]. ‘Familial X-linked hypophosphatemic rickets’ may be associated with hyperparathyroidism and joint abnormalities due to periarticular calcification [9]. This disorder may lead to pathological fractures and myopathy [10]. However, it does not to our knowledge, cause osteopenia of this degree of seventy or joint destruction with complete fusion of the carpal bones. ‘Hypophosphatemic non-rachitic bone disease’ causes less severe skeletal changes than X-linked hypophosphatemic rickets and would be an even more inappropriate diagnosis [11,12]
K. Kozlowski, S. Posen / European Journal of Radiology 37 (2001) 134–138
Some of the ‘juvenile osteoporosis syndromes’ (including various types of osteogenesis imperfecta) may give rise to crippling disabilities but not to these radiological appearances [13 –15]. ‘Malignant primary osteoporosis’ affects young and middle aged adult males exclusively. There is inexorable progression and ominous course of the disease. Loss of height, multiple spontaneous fractures and only mild skeletal pain are further characteristics of the disease. The patient of Kuhlencordt and Kruse [16,17] performed military service at the age of 19 years. At the age of 35 he lost 31 cm in height and was incapacitated.
137
‘Polyostotic fibrous dysplasia’ which may be associated with hypophosphatemic osteomalacia is characterised by the asymmetry of the skeletal lesions in affected individuals. In this patient the skin was unaffected and every tubular bone was symmetrically abnormal. The clinical course of this patient’s disease was characterised by short stature, muscle weakness and progressive, crippling skeletal deformities. There was persistent hypophosphatemia, documented hyperparathyroidism and osteomalacia but we believe that none of these conditions were responsible for the radiological abnormalities, which were so unusual that we postulate the presence of a ‘hitherto undescribed entity’.
Fig. 2. A – E: 26-year-old. Osteopenia. Generalised narrowing of all the joint spaces. A: The carpal bones present as one bony mass. B: Mushroom deformity of the epiphyseal regions with fracture at the distal end of the right femoral shaft. C: Bilateral coxa vara with marked narrowing and deformity of the pelvis. Bubble appearance of the bony pattern of the femoral heads. D: Platyspondyly with narrowing of the intervertebral disc spaces. Kyphosis of the sacrum and the coccyx. E: Irregular bony pattern of the frontal bone. Radiolucent peripheral part of the cranium. Platybasia. Hypoplastic/dysplastic teeth. Absent lamina dura.
138
K. Kozlowski, S. Posen / European Journal of Radiology 37 (2001) 134–138
The pathogenesis of this disorder is obscure. One might speculate about some mutation in one of the genes governing the differentiation of prehypertrophic chondrocytes such as the Indian hedgehog signalling pathway or the PTH/PTHrP receptor [18] though there are obviously many other possibilities.
References [1] Hayes CW, Conway WF. Hyperparathyroidism. Radiol Clin North Am 1991;29:85–96. [2] Kozlowski K, Czerminska-Kowalska A, Kulczycka H, Rowinska E, Pronicka E. Dominantly inherited isolated hyperparathyroidism: a syndromic association? Pediatr Radiol 1999;29:10– 5. [3] Scharer K, Mehls O, Gilli G. Renal bedingte skeleterkrankungen und wachstumsstorungen. Orthopede 1974;3:58–64. [4] Eastwood JB. Renal osteodystrophy — a radiological review. CRC Crit Rev Diagn Imaging 1977;1:77–104. [5] Pitt MJ. Rickets and osteomalacia are still around. Radiol Clin North Am 1991;29:97–118. [6] Lee DY, Choi IH, Lee CK, Chung CY, Cho KH. Acquired vitamin D-resistant rickets caused by aggressive osteoblastoma in the pelvis: a case report with ten years follow-up and review of the literature. J Ped Orthop 1994;14:793–8. [7] Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D. Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest 1997;99:297–304.
.
[8] Burmeister W. Das rachitische syndrome. Orthopede 1974;3:50– 7. [9] Knudtzon J, Halse J, Monn E, Nesland A, Nordal KP, Paus P, Seip M, Sund S, Sodal G. Autonomous hyperparathyroidism in X-linked hypophosphatemia. Clin Endocrinol 1995;42:199–203. [10] Reginato AJ, Falasca GF, Pappu R, McKnight B, Agha A. Musculosceletal manifestations of osteomalacia: report of 26 cases and literature review. Semin Arthr Rheumatism 1999;28:287– 304. [11] Scriver ChR, MacDonald W, Reade T. Hypophosphatemic nonrachitic bone disease: an entity distinct from X-linked hypophosphatemia in the renal defect, bone involvement and inheritance. Am J Med Genet 1977;1:101– 17. [12] Scriver ChR, Reade T, Halal F, Costa T, Cole DEC. Autosomal hypophosphataemic bone disease responds to 1,25-(OH)2D3. Arch Dis Child 1981;56:203– 7. [13] Schuster W. Osteoporose im Kindesalter 1974;3:72– 8. [14] Smith R. Idiopathic osteoporosis in the young. J Bone Joint Surg 1980;62-B:417– 27. [15] Fanconi A, Fanconi G. Eine ungewohnliche form von idiopatischer osteoporose mit hypercalcurie, kleinwuchs and schwachsinn. Helv Paediat Acta 1975;30:79– 88. [16] Kuhlencordt F, Kruse HP. Maligne primare osteoporose. Eine sonderform bei mannern im fruhen und mittleren lebensalter. Internist 1985;26:511– 20. [17] Kuhlencordt F, Kruse HP. Case report 422. Skeletal Radiol 1987;16:407– 11. [18] Lanske B, Amling M, Neff L, Guiducci J, Baron R, Kronenberg HM. Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development. J Clin Invest 1999;104:399– 407.
Case report
Malignant hypophosphathaemic bone disease K. Kozlowski *, S. Posen Departments of Radiology Royal Alexandra Hospital for Children and Endocrinology, Metabolism Royal North Shore Hospital, Sydney, Australia Received 6 March 2000; received in revised form 13 June 2000; accepted 13 June 2000
Abstract A case of crippling osteoporosis with muscular weakness, hypophosphatemia, hyperparathyroidism, defective skeletal calcification and cartilage destruction is reported. The patient, a male was observed from the age of 212 until his death at the age of 33 years. This bone/cartilage disease failed to respond to phosphate supplementation, parathyroidectomy and calcitriol. We believe this may represent a hitherto undescribed entity. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Hypophosphathemia; Rickets; Osteoporosis; Hyperparathyroidism; Cartilage destruction
1. Introduction Hypophosphatemia is a common feature of different disorders presenting as rickets. We report a patient with hypophosphatemia, observed from the age of 212 until his death at the age of 33, who presented unique clinical course and distinctive radiographic features. To the best of our knowledge no similar disorder has yet been reported.
2. Case report This boy had been born to non-consanguinous, healthy parents after an uncomplicated pregnancy. His birth weight was 3.4 kg and his three siblings were normal. He passed the usual milestones up to the age of 15 months when he presented for the evaluation of progressive right knock-knee deformity and external rotation of the right foot. These features had been noted for the past 6 months. Radiological diagnosis at the time included ‘rickets’ and ‘Jansen’s metaphyseal dysplasia’. * Corresponding author. New Children’s Hospital, PO Box 3515 Parramatta, NSW 2124, Australia. Fax: +61-2-94382562.
The legs were kept in plaster for 2 months and then in calipes for a further 12 months. At the age of 212 years his height was 85 cm, and his weight 12.7 kg. From the age of 212 years he suffered from progressive difficulties with walking and it was noted that his growth rate was decreasing. At the age of 7 years he developed progressive weakness of the lower limbs and a neurologist expressed the opinion that there was ‘generalised muscle weakness’. Various neurological investigations performed at the time (pneumoencephalography, myelography, electromyography) revealed no abnormalities. By the age of 11 years his muscular weakness and wasting had become so severe that he had to use a wheelchair for distances greater than a few steps. A fall from the wheelchair at that time resulted in a fracture of the right femoral shaft. Physical examination at that stage showed normal face, short trunk, a ‘barrel chest’ deformity, a height of 121cm, a crown –pubis distance 58 cm, and a pubis –heel distance of 63 cm and a span of 136 cm. No abnormalities were detected in the lungs, the heart or the abdomen. His mental development was considered normal. During the remainder of his life, multiple examinations confirmed the presence of muscular weakness and hypotonia. The skeletal deformities showed a gradual progression (Fig. 1A–G). He also developed flexion
0720-048X/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 7 2 0 - 0 4 8 X ( 0 0 ) 0 0 2 4 7 - 3
K. Kozlowski, S. Posen / European Journal of Radiology 37 (2001) 134–138
135
Fig. 1. A, B: 212-year-old. Osteopenia. Radiolucent metaphyses with vertical trabecular pattern. Abnormal trabecular pattern of the epiphyses and diaphyses. C: 6-year-old. Osteopenia. The radiolucent areas moved away from the shaft. Flattened epiphyses. D: 10-year-old. Osteopenia. Platyspondyly. Flattening with posterior wedging of L2 vertebral body. E: 11-year-old. Osteopenia. Radiolucent metaphyses of the forearm bones. Dense punctate and linear calcification in the phalanges resemble a little bit ‘enchondromatosis’ and support the assumption that we are dealing with an uncomplete and disturbed differentiation of chondrocytes. Flattening of the distal forearm epiphyses. F, G: 13-year-old. Osteopenia. Radiolucent metaphyses. Flattened epiphyses. Irregular trabecular pattern with multiple small cyst-like radiolucences in the metaphyses, epiphyses and round bones. Narrow cortical bone.
136
K. Kozlowski, S. Posen / European Journal of Radiology 37 (2001) 134–138
deformities of the large joints and diffuse pain of increasing severity. The pain was aggravated by movement and relieved by rest. Multiple biochemical test over the years showed persistent hypophosphatemia with values ranging from 1.2 to 2.5 mg/dl (10.4 –0.8 mmol/l). Serum calcium, other serum electrolytes and serum alkaline phosphatase were normal during the first decade of life, as were all hematological investigations. At the age of 12 years he was subjected to metabolic balance studies in the laboratory of the late Dr C.E. Dent (London) who found negative calcium and phosphate balances (− 179 and − 97 mg/day, respectively) but no other abnormalities. At the age of 14 years he was hospitalised under the care of the late Dr L.V. Avioll (St. Louis) who performed multiple investigations including fecal fat estimations, a small bowel biopsy, Ca47 absorption studies and urine acidification tests. All of these gave normal results. Abnormal results at the time included glycinuria and elevated serum alkaline phosphatase (324 U) and serum PTH concentrations (11.1 ml Eq/ml — normal 2–8), initially in the presence of normocalcemia. Serum PTH elevation persisted and serum calcium concentrations were elevated some 12 years after the initial parathyroid investigations. Nephrogenous cyclic AMP was elevated (6.36 nmol/100 ml glomerular filtrate — normal less than 1.92) at the age of 26. Repeated iliac crest biopsies were interpreted by Dr S.L. Teitelbaum to show a combination of ‘osteomalacia and osteitis fibrosa’. Treatment included phosphate supplements, calcitriol and the removal of abnormally enlarged parathyroid glands (‘hyperplasia or adenoma’) at the age of 18 and again at the age of 28. None of these measures was of any apparent benefit. Calcitriol had to be discontinued on several occasions because of symptomatic hypercalcemia. He continued to suffer from pain and weakness so that during the last few years of his life he led a bed and wheelchair existence and required increasing quantities of narcotics. Biochemical tests at the age of 32 showed a serum PTH 200 pg/ml (norm 12 – 55), a serum calcium of 2.48 mmol/l (norm 2.25 – 2.65), a serum inorganic phosphate of 0.8 mmol/l (norm 0.8 – 1.15) and a serum alkaline phosphatase of 556 U/l (norm 30 – 115). The levels of serum 25-hydroxycalciferol and 1,25 dihydroxycalciferol were normal. He became increasingly dyspneic and died at the age of 38 years of suspected respiratory failure. Serial radiographic examinations from the age of 212 years to the age of 33 years showed progressive osteopenia with transradiant metaphyses and disorganised trabecular pattern in early childhood. Later the metaphyseal transradiancy moved into the shaft of the long bones and there was washing out of the trabecular pattern. Progressive narrowing of the joint spaces with
widening of the metaphyses was most marked in the big joints and in the carpus, where it simulated carpal fusion. In the spine platyspondyly and anisospondyly secondary to osteoporosis were seen in the first decade of life. In the second and third decades, documented were progressive compression deformity of the thoracic spine and lumbar spine varying between 50 and 75%, with kyphosis of the thoracic and hyperlordosis of the lumbar spine. The skull was severely demineralised with minor, later moderately severe platybasia. There was absence of lamina dura. In the pelvis progressive acetabular protrusion, deformity of the pelvic cavity, narrowing of the hip joint space, coxa vara and unusual popcorn pattern of the femoral heads were noted (Fig. 1A–G, and Fig. 2A –E). 3. Discussion This patient’s clinical and radiographic features do not correspond to any known disorder. The distinctive abnormalities included the combination of bony and cartilaginous changes, the early onset of the disease and the progressive course, which confined the patient to a wheelchair for 27 years. The clinical and radiological abnormalities were accompanied by persistent hypophosphatemia, at first in the absence of overt hyperparathyroidism but with clear evidence of hyperparathyroidism (hypercalcaemia, elevated serum PTH, elevated nephrogenous cyclic AMP, osteitis fibrosa, enlarged parathyroid glands) at the age of 26 years. However, the skeletal changes were quite unlike those of ‘parathyroid osteopathy’ [1–4]. The histological evidence for osteomalacia was also incontrovertible. Six different specimens of bone taken from the iliac crest over the period of 12 years all showed thick osteoid seams with ‘smeared’ fluorescent labels and a total absence of double labels. These findings were noted both on and off calcitriol therapy. However the osteopenic metaphyses and the large ‘empty’ areas in the shafts of the long bones were quite unlike the radiological signs of ‘rickets’, nor were the widened metaphyses, the popcorn appearance of the proximal femoral and humeral metaphyses and marked loss of joint cartilage characteristic of ‘osteomalacia’ [5–8]. ‘Familial X-linked hypophosphatemic rickets’ may be associated with hyperparathyroidism and joint abnormalities due to periarticular calcification [9]. This disorder may lead to pathological fractures and myopathy [10]. However, it does not to our knowledge, cause osteopenia of this degree of seventy or joint destruction with complete fusion of the carpal bones. ‘Hypophosphatemic non-rachitic bone disease’ causes less severe skeletal changes than X-linked hypophosphatemic rickets and would be an even more inappropriate diagnosis [11,12]
K. Kozlowski, S. Posen / European Journal of Radiology 37 (2001) 134–138
Some of the ‘juvenile osteoporosis syndromes’ (including various types of osteogenesis imperfecta) may give rise to crippling disabilities but not to these radiological appearances [13 –15]. ‘Malignant primary osteoporosis’ affects young and middle aged adult males exclusively. There is inexorable progression and ominous course of the disease. Loss of height, multiple spontaneous fractures and only mild skeletal pain are further characteristics of the disease. The patient of Kuhlencordt and Kruse [16,17] performed military service at the age of 19 years. At the age of 35 he lost 31 cm in height and was incapacitated.
137
‘Polyostotic fibrous dysplasia’ which may be associated with hypophosphatemic osteomalacia is characterised by the asymmetry of the skeletal lesions in affected individuals. In this patient the skin was unaffected and every tubular bone was symmetrically abnormal. The clinical course of this patient’s disease was characterised by short stature, muscle weakness and progressive, crippling skeletal deformities. There was persistent hypophosphatemia, documented hyperparathyroidism and osteomalacia but we believe that none of these conditions were responsible for the radiological abnormalities, which were so unusual that we postulate the presence of a ‘hitherto undescribed entity’.
Fig. 2. A – E: 26-year-old. Osteopenia. Generalised narrowing of all the joint spaces. A: The carpal bones present as one bony mass. B: Mushroom deformity of the epiphyseal regions with fracture at the distal end of the right femoral shaft. C: Bilateral coxa vara with marked narrowing and deformity of the pelvis. Bubble appearance of the bony pattern of the femoral heads. D: Platyspondyly with narrowing of the intervertebral disc spaces. Kyphosis of the sacrum and the coccyx. E: Irregular bony pattern of the frontal bone. Radiolucent peripheral part of the cranium. Platybasia. Hypoplastic/dysplastic teeth. Absent lamina dura.
138
K. Kozlowski, S. Posen / European Journal of Radiology 37 (2001) 134–138
The pathogenesis of this disorder is obscure. One might speculate about some mutation in one of the genes governing the differentiation of prehypertrophic chondrocytes such as the Indian hedgehog signalling pathway or the PTH/PTHrP receptor [18] though there are obviously many other possibilities.
References [1] Hayes CW, Conway WF. Hyperparathyroidism. Radiol Clin North Am 1991;29:85–96. [2] Kozlowski K, Czerminska-Kowalska A, Kulczycka H, Rowinska E, Pronicka E. Dominantly inherited isolated hyperparathyroidism: a syndromic association? Pediatr Radiol 1999;29:10– 5. [3] Scharer K, Mehls O, Gilli G. Renal bedingte skeleterkrankungen und wachstumsstorungen. Orthopede 1974;3:58–64. [4] Eastwood JB. Renal osteodystrophy — a radiological review. CRC Crit Rev Diagn Imaging 1977;1:77–104. [5] Pitt MJ. Rickets and osteomalacia are still around. Radiol Clin North Am 1991;29:97–118. [6] Lee DY, Choi IH, Lee CK, Chung CY, Cho KH. Acquired vitamin D-resistant rickets caused by aggressive osteoblastoma in the pelvis: a case report with ten years follow-up and review of the literature. J Ped Orthop 1994;14:793–8. [7] Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D. Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest 1997;99:297–304.
.
[8] Burmeister W. Das rachitische syndrome. Orthopede 1974;3:50– 7. [9] Knudtzon J, Halse J, Monn E, Nesland A, Nordal KP, Paus P, Seip M, Sund S, Sodal G. Autonomous hyperparathyroidism in X-linked hypophosphatemia. Clin Endocrinol 1995;42:199–203. [10] Reginato AJ, Falasca GF, Pappu R, McKnight B, Agha A. Musculosceletal manifestations of osteomalacia: report of 26 cases and literature review. Semin Arthr Rheumatism 1999;28:287– 304. [11] Scriver ChR, MacDonald W, Reade T. Hypophosphatemic nonrachitic bone disease: an entity distinct from X-linked hypophosphatemia in the renal defect, bone involvement and inheritance. Am J Med Genet 1977;1:101– 17. [12] Scriver ChR, Reade T, Halal F, Costa T, Cole DEC. Autosomal hypophosphataemic bone disease responds to 1,25-(OH)2D3. Arch Dis Child 1981;56:203– 7. [13] Schuster W. Osteoporose im Kindesalter 1974;3:72– 8. [14] Smith R. Idiopathic osteoporosis in the young. J Bone Joint Surg 1980;62-B:417– 27. [15] Fanconi A, Fanconi G. Eine ungewohnliche form von idiopatischer osteoporose mit hypercalcurie, kleinwuchs and schwachsinn. Helv Paediat Acta 1975;30:79– 88. [16] Kuhlencordt F, Kruse HP. Maligne primare osteoporose. Eine sonderform bei mannern im fruhen und mittleren lebensalter. Internist 1985;26:511– 20. [17] Kuhlencordt F, Kruse HP. Case report 422. Skeletal Radiol 1987;16:407– 11. [18] Lanske B, Amling M, Neff L, Guiducci J, Baron R, Kronenberg HM. Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development. J Clin Invest 1999;104:399– 407.