Tumor-induced osteomalacia: the importance of early diagnosis / Osteomalácia induzida por tumor: a importância do diagnóstico precoce

Tumor-induced osteomalacia is a rare paraneoplasic syndromethat can be completely cured with the removal of the culprittumor. This study described the clinical history of a patientaffected by tumor-induced osteomalacia. The patient was a57-year-old female who sought hospital due to intense andprogressive pain in the lower limbs and muscle weakness, aswell diffuse osteoporosis and a variety of pathologic fracturesat radiographs. Laboratory tests revealed hypophosphatemiawith hyperphosphaturia and raised the hypothesis of tumorinducedosteomalacia. Whole-body technetium-99m octreotidescintigraphy revealed the presence of a focal area of radiotraceruptake in the medial region of the left tarsus. After tumorexcision, there was a rapid correction of serum phosphorus,reduction of musculoskeletal complaints and evidence of bonehealing. Despite the diagnosis and treatment, the patient hadan unfavorable clinical outcome; she developed sepsis frompulmonary focus, evolving into refractory septic shock anddeath. We stress the need for greater recognition of tumorinducedosteomalacia as a cause of clinical bone pain, fractures,osteopenia and muscle weakness, superimposed on thecharacteristic biochemical profile with hypophosphatemia andrelative hyperphosphaturia. Greater awareness of the disease willallow earlier diagnosis and ultimately a greater curative potentialfor patients afflicted with this syndrome.(AU)

Osteomalácia induzida por tumor é uma síndrome paraneoplásicarara que pode ser curada completamente com a ressecção dotumor causador. Este estudo descreveu a história clínica de umapaciente afetada pela osteomalácia induzida por tumor. Paciente,de 57 anos, deu entrada no hospital por dor em membros inferiores,e fraqueza muscular intensa e progressiva, assim comoosteoporose difusa e fraturas patológicas. Exames laboratoriaisevidenciaram hipofosfatemia com hiperfosfatúria e levantarama hipótese de osteomalácia induzida por tumor. Cintilografia detodo corpo com tecnécio-99m revelou a presença de área focalde captação do radiofármaco na região medial do tardo esquerdo.Após a ressecção do tumor, houve rápida correção do fósforosérico, redução das queixas musculoesqueléticas e evidência decalo ósseo. Apesar de diagnóstico e tratamento, a paciente apresentouum desfecho clínico desfavorável, desenvolvendo sepsede foco pulmonar, choque séptico e evoluindo a óbito. Nós enfatizamosa necessidade de maior reconhecimento da osteomaláciainduzida por tumor como causa de dor óssea, fraturas patológicas,osteopenia e fraqueza muscular, superpostos a um perfilbioquímico característico, com hipofosfatemia e hiperfosfatúriarelativa. Maior alerta sobre a doença permitirá um diagnósticomais precoce e maior potencial curativo aos pacientes afetadospor essa síndrome.(AU)

Tumor mesenquimatoso fosfatúrico de fosa nasal con compromiso intracraneano: reporte de un caso y revisión de la literatura / Nasal fossa phosphaturic mesenchymal tumor with intracraneal compromise: case report and review of the literature

El tumor mesenquimatoso fosfatúrico (TMF) es una enfermedad extremadamente rara. Según evidencia reciente es causado por la sobreexpresión del factor de crecimiento fibroblástico 23 (FGF23), el cual genera hipofosfemia y osteomalacia. A continuación presentamos el caso de un paciente de 42 años con un tumor mesenquimatoso fosfatúrico de fosa nasal izquierda con extenso compromiso intracraneano. Cabe destacar que hasta la fecha hay 142 casos reportados de TMF en la literatura de los cuales solo 11 se ubican en fosa nasaly cavidades sinusales, y sólo dos de ellos ubicados en fosa nasal¹. El paciente tuvo una exitosa resolución quirúrgica con la consecuente normalización de parámetros analíticos (incluido el FGF23), mejoría sintomática y ausenia de recidiva hasta la fecha.

The phosphaturic mesenchymal tumor (PMT) is an extremely rare disease. According to recent evidence is caused by overexpression of fibroblast growth factor 23 (FGF23) which generates hypophosphatemia and osteomalacia. We report the case of a 42 year old patient with a left nasal fossa phosphaturic mesenchymal tumor with intracranial involvement. Should be noted that to date there are 142 reported cases of PMT in the literature of which only 11 are located in nasal fossa and sinus cavities, two of them located in nasal fossa¹. The patient had a successful surgical resolution with consequent normalization of analytical parameters (including FGF23), absence of symptoms and no recurrence to date.

Efectos de la cirugía bariátrica sobre el metabolismo óseo / Effects of bariatric surgery on bone health

There is concern about the long term complications of bariatric surgery and among these, the derangements in bone metabolism that could increase the risk of osteopororosis. Most studies show an elevated bone turnover in operated patients with loss of bone mass, that are partially explained by the development of a secondary hyperparathyroidism. We have shown that, among postmenopausal women, bone resorption remains elevated, even five years after the operation, although not associated to loss of bone mass. The pathophysiology of these alterations is complex and includes an reduction in mechanical load and calcium absorption and postoperative changes in signaling hormones that have an effect on bone, coming from adipose tissue (estrogens, leptin and adiponectin), liver (insulin like growth factor-1), pancreas (insulin and amylin) or the bowel (ghrelin, glucagon-like peptide 2, peptide YY, gastric inhibitory polypeptide). Available evidence suggest that bariatric surgery should be considered a risk factor for osteoporosis. We recommend the incorporation of bone health in pre operative evaluation. We also give suggestions to prevent the adverse effects of bariatric surgery on bone health.

Osteomalacia hipofosfatémica secundaria a sarcoma de muslo: caso clínico / Hypophosphatemic osteomalacia secondary to a sarcoma: report of one case

Tumor induced osteomalacia is uncommon and is characterized by an isolated and not PTH dependent reduction in tubular phosphate reabsorption. This alteration is produced by phosphaturic factors, such as fibroblast growth factor-23 (FGF-23) that are secreted by tumors. We report a 41 years old female presenting with joint pain and progressive loss of muscle strength in the lower limbs. Initial laboratory assessment showed hypophosphatemia, elevated alkaline phosphatases, normal intact parathormone levels, low levels of 25 hydroxy vitamin D and an elevated 24 h phosphaturia. Bone mineral density showed spine and femoral neck osteopenia. A positron emission tomography (PET) revealed a right thigh tumor with lung metastases. Its biopsy disclosed a fibrosarcoma. FGF-23 levels, measured by ELISA were markedly elevated. The patient was discharged with palliative measures.

Tumor-induced osteomalacia: a case report / Osteomalácia induzida por tumor: relato de caso

Tumor-induced osteomalacia (TIO) is a rare paraneoplasic syndrome with overproduction of fibroblast growth factor 23 as a phosphaturic agent, leading to chronic hyperphosphaturia and hypophosphatemia, associated with inappropriately normal or low levels of 1,25-dihydroxyvitamin D. Diagnosis of this disease is often challenging. The following case report described a middle-aged man with symptoms of bone pain and severe muscle weakness, who was found to have TIO. The tumor responsible for the symptoms was localized on his thigh and its resection resulted in normalization of blood chemistry and complaints. Subsequent microscopic examination revealed a phosphaturic mesenchymal tumor, mixed connective tissue type. The authors reinforce the importance of recognition of this disease, as severe disability and even death can be avoided with the surgical removal of the causative tumor.

Osteomalácia induzida por tumor (OIT) é uma síndrome paraneoplásica rara, causada por hiperprodução do agente fosfatúrico, levando a hipofosfatemia e hiperfosfatúria crônicas, associadas a níveis reduzidos ou inapropriadamente normais de 1,25-dihidroxivitamina D. O diagnóstico dessa doença é, geralmente, desafiador. O relato de caso aqui apresentado descreveu um homem de meia-idade, com quadro inicial de dor óssea, fraqueza muscular extrema e hipofosfatemia, com diagnóstico tardio de OIT. O tumor responsável pelos sintomas foi localizado em membro inferior, e sua exérese resultou em normalização das alterações bioquímicas e dos sintomas. O exame microscópico da lesão revelou tumor mesenquimal fosfatúrico, tecido conectivo misto. Os autores reforçam a importância do reconhecimento dessa entidade, uma vez que a remoção do tumor responsável pelos sintomas pode evitar sérias complicações ou mesmo a morte.

A case report of tumor-induced osteomalacia: eight year followed-up.

Tumor-induced osteomalacia (TIO) is a rare but potentially curable disease. It is caused by excessive renal clearance ofphosphate induced by a substance secreted from the tumor Here, the authors report a Thai patient who presented with multiple pathologic fractures, low serum phosphorus, and low tubular maximum reabsorption of phosphorus/glomerular filtration rate (TmPO4/GFR). The clinical, biochemical and bone abnormalities improved 6 months after the surgery. Two years follow-up showed no recurrence of the disease. Physicians should be aware of this condition when encountering with adult onset osteomalacia.

Oncogenic osteomalacia.

A 59-year-old gentleman presented with symptoms of progressively worsening low back pain associated with difficulty in rising from a squat over a period of two years. Biochemical tests confirmed the initial clinical diagnosis of osteomalacia. Blood pool scanning revealed a focal hot spot on the site of the clinically visible swelling close to the metacarpo-phalangeal joint of the left index finger. The biopsy of the specimen obtained by excision was reported to be consistent with a phosphaturic mesenchymal tumour. The patient had complete resolution of symptoms six months following excision of the lesion.

Vitamin D deficiency: a global perspective / Deficiência de vitamina D: uma perspectiva global

Vitamin D is essential for the maintenance of good health. Its sources can be skin production and diet intake. Most humans depend on sunlight exposure (UVB 290­315 nm) to satisfy their requirements for vitamin D. Solar ultraviolet B photons are absorbed by the skin, leading to transformation of 7-dehydrocholesterol into vitamin D3 (cholecalciferol). Season, latitude, time of day, skin pigmentation, aging, sunscreen use, all influence the cutaneous production of vitamin D3. Vitamin D deficiency not only causes rickets among children but also precipitates and exacerbates osteoporosis among adults and causes the painful bone disease osteomalacia. Vitamin D deficiency has been associated with increased risk for other morbidities such as cardiovascular disease, type 1 and type 2 diabetes mellitus and cancer, especially of the colon and prostate. The prevalence of hypovitaminosis D is considerable even in low latitudes and should be taken into account in the evaluation of postmenopausal and male osteoporosis. Although severe vitamin D deficiency leading to rickets or osteomalacia is rare in Brazil, there is accumulating evidence of the frequent occurrence of subclinical vitamin D deficiency, especially in elderly people.

A vitamina D é essencial para a manutenção da saúde. A sua fonte principal é a pele ou pode ser ingerida com a dieta. A maioria dos seres humanos depende da exposição solar para adquirir quantidades suficientes de vitamina D. A radiação ultravioleta tipo B transforma o 7-dehidrocolesterol em vitamina D3 (colecalciferol). A época do ano, latitude, pigmentação da pele, idade e uso de filtros solares são fatores que influenciam a produção cutânea. Deficiência de vitamina D pode causar raquitismo e osteomalacia, exacerbar a perda óssea na osteoporose, como também pode associar-se a várias morbidades como doenças cardiovasculares, diabetes mellitus tipo 1 e 2, câncer de próstata e de intestino grosso. A prevalência de hipovitaminose D tem sido relatada com grande freqüência mesmo em regiões de baixa latitude e deve ser considerada na avaliação da osteoporose. Embora a deficiência severa levando a osteomalacia possa ser vista raramente no Brasil, evidências se acumulam da freqüente ocorrência de deficiência subclínica, especialmente em idosos.

[Study of 52 cases of osteomalacia]

Osteomalacia is a disorder of bone mineralization secondary to Vitamin D deficiency. Clinical presentation and related parameters in 52 cases and their treatment discussed. This is a discriptive study of patients with osteomalacia which is performed at the departments of rheumatology and endocrines, Mashhad Medical Sciences University. Patients were diagnosed according to clinical presentation, radiological findings, blood tests, and bone biopsy if necessary. Patients were treated either orally with 0/25 micro g Calcitriol or as IM injection of vitamin-D [300000 units]. For the prevention of recurrence, injection was repeated every 6-12 months. Older patients were also recommended to expose themselves to ultraviolet radiation 2-3 times every week. All findings were recorded and later processed using statistical tests. From the 52 patients, 47 were women [90%] and 5 were men [10%]. Clinical presentations were back pain, fatigue and bone tenderness especially in lumbar area, osteopenic symptoms, and gait disorder. 44 patients had Looser's zone which is diagnostic of osteomalacia Based on calculated statistics, a significant reduction in serum Calcium [P< 0.005], phosphorus [P< 0.002], and increased Alkaline phosphatase [P< 0.002] and parathyroid hormone [P< 0.004] was observed. Most of our patients were admitted during winter and early sprin. The disease was more common in young women [age 10-19] than women older than 30 years of age [P< 0.004]. Patients with Vitamin D deficiency were alleviated by Vitamin D treatment. Osteomalacia exists as a silent disease in north east of Iran. The main cause of this is considered to be vitamin D deficiency. Therefore, preventive measures are to be taken

Phosphaturic mesenchymal tumor: a case report.

Osteomalacia induced by tumor is a rare phenomenon in which the resection of tumor is followed by dramatic amelioration of clinical signs and symptoms. We hereby report a case of a 66 years old male who presented with features of osteomalacia in which the characteristic clinical presentation was associated with the phosphaturic mesenchymal tumor, mixed connective tissue variant. The case is reported for its rarity.

Hipofosfatemia revertida al extirpar hemangioendotelioma compuesto del dedo mayor del pie / Reversion of hypophosphatemia after the excision of a composite hemangioendothelioma in the great toe

We report a 43 years old male admitted to the hospital for progressive lumbar pain, lasting 20 years, that caused severe disability. On admission the patient had a serum phosphate of 2 mg/dl, an urine phosphate excretion over 300 mg/dl and serum alkaline phosphatases over 750 U/L. Serum intact parathormone was normal and tubular maximum phosphorus/glomerular filtration was 0.7 mg/dl. Bone scintigraphy showed an increased radionuclide uptake in condro-costal joints. Bone densitometry showed femoral osteoporosis. A violet colored mass was detected in a great toe. It was removed and the pathological diagnosis was a composite hemangioendothelioma. After tumor excision, serum phosphate levels returned to normal values and symptoms disappeared within 15 days.

Papel da histomorfometria óssea no diagnóstico diferencial da osteomalacia / Role of bone histomorphometry in the differential diagnosis of osteomalacia

A osteomalacia é uma doença ósteo-metabólica em que há deficiente mineralização do osso, e é definida pela histomorfometria óssea por apre-sentar espessura do rebordo osteóide (O.Th) maior do que 15µm, e inter-valo de tempo para mineralização (MLT) maior do que 100 dias. As princi-pais etiologias de osteomalacia são a deficiência de ação da vitamina D e a hipofosfatemia. Neste trabalho, 14 pacientes com osteomalacia diag-nosticados clínica e laboratorialmente foram divididos em dois grupos: 6 pacientes com deficiente ação de vitamina D e 8 hipofosfatêmicos. Todos os pacientes apresentaram ao exame histomorfométrico aumento do O.Th e do MLT compatível com o diagnóstico de osteomalacia. A superfície de reabsorção óssea estava aumentada no grupo com defi-ciência de ação da vitamina D. Em seis pacientes hipofosfatêmicos, a superfície de reabsorção óssea estava ausente, em um paciente dentro da normalidade mas em um paciente encontrava se aumentada. Con-clusão: a histomorfometria dinâmica óssea através da análise dos parâmetros de formação confirmam o diagnóstico de osteomalacia, enquanto que os parâmetros de reabsorção permitem uma orientação etiológica.

Osteomalacia - A commonly misdiagnosed cause of gait difficulty

Osteomalacia is a metabolic bone disorder caused by deficiency of Vitamin D and its active metabolites. We report 46 cases of Osteomalacia diagnosed on the basis of clinical features of bone pain, gait difficulty and muscle weakness, plus biochemical findings of a low or normal serum calcium, low phosphorus and raised serum alkaline phosphatase level. Urinary calcium, phosphorus and serum paratharmone levels were also estimated in a few cases. Radiologic features included a typical fuzziness of bone architecture and Looser's zones. Out of 46 cases, 4 were males and 42 females. Age ranged from 13 to 45 years. In 3 males disease was attributed to drugs [Phenytoin, and Carbamazepine] and one to renal osteodystrophy. Out of the 42 female patients 4 were diagnosed as Renal Tubular Acidosis, 3 had Neurofibromatosis associated with Osteomalacia, 1 had malabsorption with Crohn's disease, 2 had hypophosphataemic Osteomalacia, and 2 were diagnosed to be associated with drugs [Rifampicin, Phenytoin and Phenobarbitone]. Eight female patients had onset of symptoms during or after pregnancy [mostly multiparous]. 10 female patients had history of deprivation of sunshine and low Vitamin D diet [deprivational Osteomalacia]. In 12 female patients cause could not be ascertained despite search. All showed good responses to Vitamin D or its analogues. The time between the onset of symptoms and presentation to the department of Neurology where they were diagnosed varied from 1 to 4 years. It is essential that the awareness level of the medical community be raised so that unnecessary morbidity from Osteomalacia may be prevented

Raquitismo e osteomalacia / Rickets and osteomalacia

Raquitismo e osteomalacia são defeitos da mineralização óssea. O raquitismo é caracterizado por anormalidades na formação na placa epifisária de crescimento, com áreas não mineralizados, desorganização da arquitetura celular e retardo na maturação óssea. A osteomalacia é caracterizada pela deficiente mineralização da matriz osteóide do osso cortical e trabecular com acúmulo do tecido osteóide pouco mineralizado. São processos que, em geral, ocorrem associados. Após o final do crescimento, com o fechamento da cartilagem epifisária, apenas a osteomalacia permanece. A folha do processo de mineralização tem como uma das principais causas a inadequada concentração extracelular de cálcio e fósforo, os dois principais componentes minerais do osso, e a falta ou comprometimento da ação dos elementos responsáveis pela sua absorção, principalmente a vitamina D. As principais manifestações clínicas como as deformidades ósseas e o atraso no crescimento, são semelhantes nos diferentes tipos de raquitismo e osteomalacia existem características que são específicas. As causas são adquiridas ou hereditárias e os recentes avanços em biologia molecular permitem a identificação dos genes envolvidos e das mutações. Essa discussão inclui os principais tipos da patologia.

Osteomalacia--fifty five patients seen in a teaching institution over a 4 year period.

A retrospective analysis of 55 cases of osteomalacia shows that poor calcium intake and poor sunlight exposure are the most common causes for osteomalacia. However, in patients with normal nutritional history, other disorders such as renal tubular acidosis and tumour induced osteomalacia should be looked for. A careful drug history, particularly anticonvulsant use is essential. In 4 patients there was an association between anti-tuberculous drug use and osteomalacia. Further prospective studies are needed to determine the relationship between Rifamicin use and osteomalacia.

Oncogenic osteomalacia: a clinicopathologic study of 17 bone lesions

Oncogenic osteomalacia is an unusual and rare clinicopathologic syndrome characterized by mesenchymal tumors that apparently produce osteomalacia and biochemical abnormalities consisting of hypophosphatemia, normocalcemia, and increased levels of alkaline phosphatase. We collected from the Mayo Clinic files and from our consultation files the records for 17 cases of osteomalacia associated with bone lesions. There were five cases of fibrous dysplasia, three of hemangiopericytoma, and two of phosphaturic mesenchymal tumor. There was one case each of osteosarcoma, chondroblastoma, chondromyxoid fibroma, malignant fibrous histiocytoma, giant cell tumor, metaphyseal fibrous defect, and hemangioma. In this study we can figure out that the most common characteristic histologic features of our cases were hemangiopericytomatous vascular proliferation, fine lace-like stromal calcification, and stromal giant cells. In most of the cases, the clinical and biochemical symptoms and signs resolved soon after complete resection of the lesion. When the lesion recurred or metastasized, the symptoms and signs also recurred.

Tumour induced osteomalacia: a report of two cases. A disease of defective matrix synthesis?

Tumour induced hypophosphataemic osteomalacia or rickets is a well delineated clinical entity. There is confusion, however, about the nomenclature and classification of the associated tumours. The tumour factor responsible for the biochemical abnormalities has also not been identified. We report here two cases: one, a 43 year old male with a soft tissue tumour in the left vastus medialis, and the other, a 25 year old female with a soft tissue tumour in the right anterior axillary fold. Reversal of biochemical abnormalities and clinical improvement occurred after removal of the tumour in both cases. Both tumours showed unusual morphology characterised by spindle cell component, large vascular spaces, osteoclast-like giant cells, calcification and ossification. The tumour in the second patient was benign, while the nature of the tumour in the first patient was debated. We speculate that defective matrix may be the cause of unusual histology of the tumours, and also the source of the phosphaturic factor.