Elevated serum FGF23 concentrations in plasma cell dyscrasias

Stewart, Inge; Roddie, Claire; Gill, Anthony J.; Clarkson, Adele; Mirams, Michiko; Coyle, Luke; Ward, Christopher; Clifton-Bligh, P; Robinson, Bruce G.; Mason, Rebecca S.; Clifton‐Bligh, Roderick

doi:10.1016/j.bone.2006.01.163

Cited by 25 publications

(26 citation statements)

References 54 publications

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“…However, both Fgf23 −/− and Klotho −/− (148, 155) showed thymic atrophy and a reduced number of splenocytes, indicating that FGF23 signaling could influence hematopoiesis. Given that FGF23 is physiologically expressed in the thymus and that FGF23 is elevated in plasma cell dyscrasias (190), this suggests that FGF23 may well play a role in lymphopoiesis and hematopoiesis. Moreover, high doses of FGF23 can induce proliferation of murine bone marrow-derived pro-B cell lines (228), since Klotho is reported absent in lymphatic organs including bone marrow, thymus, and spleen (148).…”

Section: Fgf23 Functionmentioning

confidence: 99%

“…Theoretically, high rates of bone turnover would release calcium and phosphate from bone, leading to calcium-mediated suppression of PTH and elevated FGF23 preventing hyperphosphatemia. There is an association of increased FGF23 and plasma cell dyscrasias (190), but a formal assessment of the effect of increased osteoclastic mediated bone resorption of FGF23 expression in bone has not been performed. It is also possible that the discrepancies between PTH lack of a direct effect on FGF23 promoter activity and the apparent ability of intermittent versus continuous administration of PTH to respectively inhibit and stimulate FGF23 may be due to primary effects of PTH to affect bone remodeling.…”

Section: Fgf23 Regulationmentioning

confidence: 99%

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Regulation and Function of the FGF23/Klotho Endocrine Pathways

Martin

David

Quarles

2012

Physiological Reviews

505

437

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Calcium (Ca2+) and phosphate (PO43−) homeostasis are coordinated by systemic and local factors that regulate intestinal absorption, influx and efflux from bone, and kidney excretion and reabsorption of these ions through a complex hormonal network. Traditionally, the parathyroid hormone (PTH)/vitamin D axis provided the conceptual framework to understand mineral metabolism. PTH secreted by the parathyroid gland in response to hypocalcemia functions to maintain serum Ca2+ levels by increasing Ca2+ reabsorption and 1,25-dihydroxyvitamin D [1,25(OH)2D] production by the kidney, enhancing Ca2+ and PO43− intestinal absorption and increasing Ca2+ and PO43− efflux from bone, while maintaining neutral phosphate balance through phosphaturic effects. FGF23 is a recently discovered hormone, predominately produced by osteoblasts/osteocytes, whose major functions are to inhibit renal tubular phosphate reabsorption and suppress circulating 1,25(OH)2D levels by decreasing Cyp27b1-mediated formation and stimulating Cyp24-mediated catabolism of 1,25(OH)2D. FGF23 participates in a new bone/kidney axis that protects the organism from excess vitamin D and coordinates renal PO43− handling with bone mineralization/turnover. Abnormalities of FGF23 production underlie many inherited and acquired disorders of phosphate homeostasis. This review discusses the known and emerging functions of FGF23, its regulation in response to systemic and local signals, as well as the implications of FGF23 in different pathological and physiological contexts.

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Section: Fgf23 Functionmentioning

confidence: 99%

Section: Fgf23 Regulationmentioning

confidence: 99%

Regulation and Function of the FGF23/Klotho Endocrine Pathways

Martin

David

Quarles

2012

Physiological Reviews

505

437

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“…In some studies [7, 8], FGF23 levels were determined by immunoassay before and after tumor resection. These reports concluded that FGF23 is increased in many patients of osteomalacia prior to tumor resection.…”

Section: Discussionmentioning

confidence: 99%

A Case of Acute Prosthesis Migration after Femoral Head Replacement due to Osteomalacia by FGF23-Induced Tumor

Hayashi

Nishiyama

Fujishiro

et al. 2012

Case Reports in Medicine

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Fibroblast growth factor 23 (FGF23) was recently identified as an important factor involved in the development of hypophosphatemic rickets and osteomalacia. We experienced a rare case of acute prosthesis migration after hemihip arthroplasty due to FGF23-induced tumor. The patient underwent femoral head replacement because of femoral neck fracture, but prosthesis migration was occurred at 1 week after operation. The patient took various examinations, and FGF23-induced tumor was found in his right wrist. The tumor was resected, and he underwent total hip arthroplasty 8 month later. Finally, he was able to obtain free gait without pain.

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“…This disorder can, however, rarely be associated with carcinomas of epidermal and endodermal origin, 4 multiple myeloma and chronic lymphatic leukaemia. 5 A diligent search for an underlying tumour is therefore indicated. If identified, tumour resection should lead to complete symptomatic and biochemical improvement.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic hypophosphataemic osteomalacia mimicking bone metastases on isotope bone scan

Dowman

Khattak

2006

Annals of the Rheumatic Diseases

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A 61-year-old man presented with an 18-month history of musculoskeletal pain affecting the dorsolumbar spine, ribs and thighs, and a 6-month history of pain and swelling of the left foot. Examination showed rib tenderness, and mild swelling and tenderness of the left foot. The only abnormality detected on initial investigations was a raised alkaline phosphatase of level 266 U/l (normal range 37-170 U/l). Plain radiographs of the lumbar spine and foot were normal, but an isotope bone scan showed extensive hot spots in the left foot and in the ribs bilaterally, which were highly suggestive of metastases (fig 1).An extensive search for malignancy was negative. Serum levels of 25 hydroxyvitamin D 3 (25,OHD 3 ), parathyroid hormone and calcium were normal, but serum phosphate was consistently low (0.5-0.7 mmol/l). Further, vitamin D 3 analysis showed a low 1,25(OH) 2 D 3 (calcitriol) level of 16 pg/ml (normal range 20-50 pg/ml). This biochemical profile of normal 25,OHD 3 , calcium and parathyroid hormone levels with hypophosphataemia and low serum 1,25(OH) 2 D 3 is characteristic of oncogenic hypophosphataemic osteomalacia. Treatment with oral calcitriol and phosphate led to the complete resolution of symptoms and isotope bone scan abnormalities over 6-12 months. Almost 5 years later, we have not identified any tumour, and the patient remains on calcitriol and phosphate. DISCUSSIONOncogenic hypophosphataemic osteomalacia is a rare paraneoplastic syndrome due to renal phosphate wasting.1 It is characterised by hypophosphataemia, excessive urinary phosphate excretion and reduced 1,25(OH) 2 D 3 but normal 25,OHD 3 levels. Although the exact mechanism causing this abnormality is not proven, studies have suggested that this biochemical picture is caused by a circulating phosphaturic factor released by the tumour, which inhibits 1a-hydroxylase, the enzyme responsible for the conversion of 25,OHD 3 into 1,25(OH) 2 D 3 . Fibroblast growth factor 23 may be implicated.2 A similar biochemical abnormality is found in X-linked hypophosphataemic osteomalacia of infancy. 3The traditional name for this disorder connoting its classification as a paraneoplastic phenomenon is slightly misleading, 3 as most of the tumours associated with oncogenic hypophosphataemic osteomalacia are benignandmesenchymal in nature. This disorder can, however, rarely be associated with carcinomas of epidermal and endodermal origin, 4 multiple myeloma and chronic lymphatic leukaemia. 5 A diligent search for an underlying tumour is therefore indicated. If identified, tumour resection should lead to complete symptomatic and biochemical improvement. However, if it is not possible to identify the culprit tumour, as in our patient, the patient will need pharmacological treatment with phosphate and calcitriol and long-term surveillance, as oncogenic hypophosphataemic osteomalacia may present several years before the tumour source is identified.

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Elevated serum FGF23 concentrations in plasma cell dyscrasias

Cited by 25 publications

References 54 publications

Regulation and Function of the FGF23/Klotho Endocrine Pathways

Regulation and Function of the FGF23/Klotho Endocrine Pathways

A Case of Acute Prosthesis Migration after Femoral Head Replacement due to Osteomalacia by FGF23-Induced Tumor

Oncogenic hypophosphataemic osteomalacia mimicking bone metastases on isotope bone scan

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