Marked increase in bone mineral density with oral phosphate and calcitriol in tumour-induced osteomalacia.

Patients with osteomalacia have a low bone mineral density (BMD) and are often misdiagnosed as osteoporosis. A marked increase in BMD is noticed following successful treatment of osteomalacia. The biochemical hallmark of tumour-induced osteomalacia (TIO) is hypophosphatemia. Patients with TIO often have severe hypophosphatemic osteomalacia and dual-energy X-ray absorptiometry may demonstrate low BMD. Surgical removal of the phosphatonin-secreting lesion restores serum phosphate, corrects osteomalacia and is associated with a dramatic increase in BMD. We report two patients with TIO and low BMD, who were treated with oral phosphate and calcitriol supplementation. The percentage increase in BMD at 33 months was as high as 94.3% in areas with the lowest BMD at baseline. The BMD at 33 months was higher than the +2SD of the population-specific reference ranges, a finding not reported in surgically treated patients with TIO. An intermittent rise in parathyroid hormone following oral phosphate supplementation might have resulted in such findings.

Vitamin D Deficiency in Chronic Childhood Disorders: Importance of Screening and Prevention.

Vitamin D plays a vital role in regulating calcium and phosphate metabolism and maintaining bone health. A state of prolonged or profound vitamin D deficiency (VDD) can result in rickets in children and osteomalacia in children and adults. Recent studies have demonstrated the pleiotropic action of vitamin D and identified its effects on multiple biological processes in addition to bone health. VDD is more prevalent in chronic childhood conditions such as long-standing systemic illnesses affecting the renal, liver, gastrointestinal, skin, neurologic and musculoskeletal systems. VDD superimposed on the underlying disease process and treatments that can adversely affect bone turnover can all add to the disease burden in these groups of children. The current review outlines the causes and mechanisms underlying poor bone health in certain groups of children and young people with chronic diseases with an emphasis on the proactive screening and treatment of VDD.

[Hip fracture due to osteomalacia secondary to celiac disease] / Fractura de cadera debida a osteomalacia secundaria a enfermedad celíaca

Background: Hip fracture in the young patient is uncommon, but it can have devastating consequences. This pathology in the context of minimal trauma obliges us to carry out a study on calcium metabolism to determine the primary cause. Material and methods: We present a clinical case about an 18-year-old male patient who suffered a subcapital fracture of the left hip due to minimal trauma while playing football. The patient was treated urgently by means of closed reduction and internal fixation with two spongy screws. Subsequently, the metabolism study showed a severe vitamin D deficiency (27.1 nmol/L - normal above 75 nmol/L) and high levels of anti-transglutaminase IgA antibodies (2502.40 U/mL). The digestive biopsy confirmed the diagnosis of celiac disease and was treated with a gluten-free diet and calcium and vitamin D supplements. Results: After two years of follow-up, the patient is pain free, with complete hip mobility. There have been no complications (failure of osteosynthesis, avascular necrosis or pseudoarthrosis) and serum levels of vitamin D as well as IgA antibodies against transglutaminase have normalized. Conclusion: In young patients with low energy trauma fractures, vitamin D deficiency must be considered as a possible etiology and the reason for such osteomalacia, such as celiac disease, must be identified.

Antecedentes: La fractura de cadera en el paciente joven es infrecuente, pero puede tener unas consecuencias devastadoras. Esta patología en el contexto de un traumatismo mínimo nos obliga a realizar un estudio sobre el metabolismo del calcio para filiar la causa primaria. Material y método: Presentamos un caso clínico sobre un paciente varón de 18 años que sufrió una fractura subcapital de cadera izquierda debido a un traumatismo mínimo mientras jugaba al fútbol. El paciente fue tratado quirúrgicamente de urgencia mediante reducción cerrada y fijación interna con dos tornillos de esponjosa. Posteriormente, el estudio del metabolismo mostró una deficiencia grave de vitamina D (27.1 nmol/L ­ normal por encima de 75 nmol/L) y altos niveles de anticuerpos IgA antitransglutaminasa (2502.40 U/mL). La biopsia digestiva confirmó el diagnóstico de enfermedad celíaca por lo que fue tratado con una dieta libre de gluten y suplementos de calcio y vitamina D. Resultados: Tras dos años de seguimiento, el paciente está libre de dolor, con movilidad completa de la cadera. No ha habido complicaciones (fracaso de la osteosíntesis, necrosis avascular o pseudoartrosis) y los niveles séricos de vitamina D así como de los anticuerpos IgA antitransglutaminasa se han normalizado. Conclusión: En pacientes jóvenes que presentan fracturas por traumatismos de baja energía, se ha de tener en cuenta la deficiencia de vitamina D como posible etiología y se debe identificar el motivo de dicha osteomalacia, como es la enfermedad celíaca. Conclusión: En pacientes jóvenes que presentan fracturas por traumatismos de baja energía, se ha de tener en cuenta la deficiencia de vitamina D como posible etiología y se debe identificar el motivo de dicha osteomalacia, como es la enfermedad celíaca.

Vitamin D and Cardiovascular Disease: An Updated Narrative Review.

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

Nutritional rickets & osteomalacia: A practical approach to management.

Defective mineralization of the growth plate and preformed osteoid result in rickets and osteomalacia, respectively. The leading cause of rickets worldwide is solar vitamin D deficiency and/or dietary calcium deficiency collectively termed as nutritional rickets. Vitamin D deficiency predominates in high-latitude countries in at-risk groups (dark skin, reduced sun exposure, infants and pregnant and lactating women) but is emerging in some tropical countries due to sun avoidance behaviour. Calcium deficiency predominates in tropical countries, especially in the malnourished population. Nutritional rickets can have devastating health consequences beyond bony deformities (swollen wrist and ankle joints, rachitic rosary, soft skull, stunting and bowing) and include life-threatening hypocalcaemic complications of seizures and, in infancy, heart failure due to dilated cardiomyopathy. In children, diagnosis of rickets (always associated with osteomalacia) is confirmed on radiographs (cupping and flaring of metaphyses) and should be suspected in high risk individuals with the above clinical manifestations in the presence of abnormal blood biochemistry (high alkaline phosphatase and parathyroid hormone, low 25-hydroxyvitamin D and calcium and/or low phosphate). In adults or adolescents with closed growth plates, osteomalacia presents with non-specific symptoms (fatigue, malaise and muscle weakness) and abnormal blood biochemistry, but only in extreme cases, it is associated with radiographic findings of Looser's zone fractures. Bone biopsies could confirm osteomalacia at earlier disease stages, for definitive diagnosis. Treatment includes high-dose cholecalciferol or ergocalciferol daily for a minimum of 12 wk or stoss therapy in exceptional circumstances, each followed by lifelong maintenance supplementation. In addition, adequate calcium intake through diet or supplementation should be ensured. Preventative approaches should be tailored to the population needs and incorporate multiple strategies including targeted vitamin D supplementation of at-risk groups and food fortification with vitamin D and/or calcium. Economically, food fortification is certainly the most cost-effective way forward.

Severe, reversible dysphagia and malnutrition in a patient with tumour-induced hypophosphataemia.

Up to 20% of hospitalised patients may have low serum phosphate concentrations. In certain groups, such as patients with chronic alcohol overconsumption, severe trauma or sepsis, the prevalence may be 30%-50%. Profound hypophosphataemia is less common, but may lead to severe physiological disturbances. In rare cases, hypophosphataemia is caused by phosphaturic substances excreted from a tumour. Osteomalacia with chronic bone pain and fractures, as well as muscle weakness, is common in such patients. The tumours are often small and difficult to detect. Studies suggest that fibroblast growth factor 23 is a reliable marker for detection of these tumours. Persistent hypophosphatemia unresponsive to supplements should raise clinical alertness. With complete resection of the neoplasm, the symptoms rapidly reverse. If the tumour cannot be removed, treatment relies on supplementation with phosphate and active vitamin D compounds. We present a case report of a patient with severe hypophosphataemia, osteomalacia, dysphagia and malnutrition.

Sjögren's Syndrome Associated with Fanconi's Syndrome and Osteomalacia.

BACKGROUND Sjögren's syndrome is a chronic inflammatory autoimmune disease, which is also known as sicca syndrome, due to the symptoms of dry eyes and dry mouth, and is associated with other connective tissue diseases and autoimmune diseases. Sjögren's syndrome can also be associated with renal involvement. Fanconi's syndrome is associated with impaired reabsorption in the proximal renal tubule associated with tubulointerstitial nephritis and is associated with renal tubular acidosis and hypophosphatemia. Osteomalacia is a rare association with Sjögren's syndrome, which may result from renal disease. CASE REPORT We report the case of a 34-year-old woman who presented with xerostomia, xerophthalmia, bone fractures, and osteomuscular pain. A Schirmer test showed reduced tear production, and a biopsy of a minor salivary gland of the lip, with high titers of antinuclear antibodies (ANA), and positive anti-SSA/Ro and anti-SSB/La antibodies confirmed the diagnosis of Sjögren's syndrome. Serum and urinary laboratories tests and clinical manifestations confirmed Fanconi's syndrome associated with osteomalacia. The patient was treated with potassium supplements, 25-hydroxyvitamin D (25(OH)D), hydroxychloroquine, mycophenolate mofetil, and prednisone, with a favorable response. CONCLUSIONS This case is of a rare association between Sjögren's syndrome, Fanconi's syndrome, and osteomalacia. Even though these are rare clinical associations, early detection can improve the quality of life and prevent further complications.

[Vitamin D - a geriatric point of view].

Elderly people more often suffer from vitamin D insufficiency. It is caused by insufficient supply with diet and scarce sun exposure, due to life style. This is a very common situation in Poland and worldwide. Vitamin D influences functioning of many various organs. Its deficiency may cause bone mineralization disorders, osteomalacia, osteoporosis, muscle weakening, which can result in higher risk of falls. Its influence on cardiovascular diseases, type 2 diabetes and cognitive functions is widely discussed. Supplementation is crucial in elderly population. It should be administrated all year, with adjustement of dose to age and weight. Initial blood concentration is not required. An appropriate sun exposure is recommended. Treatment of vitamin D deficiency should be intensive and last for several months. Although the doses are high, no adverse effects were observed.

Osteomalacia en un adulto joven / Osteomalacia in a young adult

Los cuadros de osteomalacia hipofosfatémica responden a diversas causas genéticas y adquiridas. Algunas variantes de tumores mesenquimales producen cantidades inapropiadas de factor de crecimiento fibroblástico 23 (FGF-23), un mediador que induce una pérdida renal de fosfatos. El cuadro bioquímico se caracteriza por hipofosfatemia, disminución de la reabsorción tubular de fosfatos, niveles bajos o inapropiadamente normales de calcitriol sérico y niveles altos o inapropiadamente normales de FGF-23 plasmático. Este síndrome paraneoplásico es denominado osteomalacia tumoral u oncogénica. Existen limitadas series de casos publicadas, pero su reconocimiento es creciente en los últimos años. El diagnóstico puede ser complejo por su baja incidencia, la dificultosa localización de los tumores y la heterogeneidad en la interpretación histopatológica. La exéresis quirúrgica completa es curativa, pero puede haber recidivas y los suplementos orales de fósforo y calcitriol son alternativas de tratamiento médico (AU)

Cases of hypophosphatemic osteomalacia respond to various causes, both genetic and acquired. Some variants of mesenchymal tumors produce inappropriate amounts of fibroblast growth factor 23 (FGF-23), a mediator which induces renal phosphate loss. The biochemical picture is characterized by hypophosphatemia, decreased tubular reabsorption of phosphates, low or inappropriately normal serum calcitriol and high or unusually normal levels of FGF-23 plasma. This paraneoplastic syndrome is called tumorinduced or oncogenic osteomalacia. There are a limited series of published cases, although it has been increasingly accepted in recent years. Diagnosis may be complex given its low incidence, the difficulties in localizing the tumors and heterogeneity in histopathologic interpretation. Complete surgical removal has healed, but there may be recurrences whereas phosphorus and calcitriol oral supplements offer alternative medical treatment (AU)

A case of hypophosphatemic osteomalacia secondary to deferasirox therapy.

Patients with ß-thalassemia major require iron-chelation therapy to avoid the complication of iron overload. Until recently, deferoxamine (DFO) was the major iron chelator used in patients requiring chronic hypertransfusion therapy, but DFO required continuous subcutaneous therapy. The availability of deferasirox (Exjade®), an orally active iron chelator, over the past 4 years represented a necessary alternative for patients requiring chelation therapy. However, there have been increasing reports of proximal renal tubular dysfunction and Fanconi syndrome associated with deferasirox in the literature. We report a case of hypophosphataemic osteomalacia secondary to deferasirox therapy.

Bone disorders in chronic liver diseases.

Bone disease is a major complication of chronic liver disease. Osteomalacia is quite uncommon despite low vitamin D levels in the majority of patients with cirrhosis. In contrast, osteoporosis is quite common, occurring in up to 50% of patients. Osteoporosis can result in spontaneous or low-impact fractures in patients with chronic liver diseases, adversely affecting morbidity, quality of life, and survival. The general biology of osteoporosis, including its pathogenesis, diagnostic tools, and rationale for treatment, have been determined largely empirically from studies of postmenopausal women with osteoporosis. Treatment regimens with modification of risk factors, use of vitamin D, and supplementation with calcium and bisphosphonates have been shown to be effective in select groups of patients with chronic liver diseases.

[Glucocorticoid-induced osteoporosis]. / Osteoporoza posteroidowa.

Long-term treatment with glucocorticoids can result in drug-related complications, among which osteoporosis is one of the most frequently encountered problems. Each patient treated with a dose of 7.5 mg or more of prednisone daily for at least 3 months can be affected. During the prolonged steroid use bone formation is inhibited while its resorption increases and negative calcium balance with secondary hyperparathyroidism occurs. In the affected bone, multiple focuses of osteomalacia and avascular necrosis are also described. The bone fracture risk is much higher than it can be suspected on the basis of bone mineral density (BMD) assessment. Therefore, in glucocorticoid-treated patients with only slightly decreased BMD (osteopenia according to the WHO criteria) treatment with antifracture agents should be initiated as soon as possible. Indication for therapy is a T-score of -1.5. Calcium supplementation with vitamin D represents an initial step of prevention and treatment. A first-line treatment effective in preventing bone fractures involves aminobisfosfonates such as alendronate and risedronate. Other effective agents are also estrogens, testosterone, selective estrogen receptor modulators and anabolic agents (parathormon, dehydroepiandrosteron, strontium ranelate).

Pseudofracture of the neck of femur secondary to osteomalacia.

Nutritional osteomalacia is a metabolic bone disorder common among the Asian female immigrant population in the United Kingdom. We describe the case of a female of Asian origin, who was found to have a unilateral undisplaced pseudofracture of the neck of the femur during pregnancy. Although not operated on the fracture was treated successfully with calcium and vitamin D supplement therapy. Within one month of treatment, the bone pain subsided and she was able to bear full weight. Subsequent radiological follow-up showed the pseudofracture to have healed sufficiently with no evidence of avascular necrosis. There should be a high index of suspicion of this disease, particularly among Asian patients presenting with persistent and non-specific musculoskeletal pain.

Déficit de vitamina D y osteomalacia en ancianos no institucionalizados con fractura de cadera / Vitamin D deficiency and osteomalacia in non-institutionalised elderly individuals with hip fracture

Objetivo: determinar la prevalencia del déficit de vitamina D en un grupo de ancianos con fractura de cadera en comparación con controles de similar edad, y analizar si presentan mayor riesgo de fractura. Secundariamente se estudia su potencial relación con la sospecha de osteomalacia «clínica y bioquímicamente probable». Material y métodos: estudio prospectivo y descriptivo de 68 ancianos no institucionalizados con independencia funcional previa, que ingresan por fractura de cadera. Se les realizan historia clínica, toma de muestra sanguínea de calcio, fósforo, 25-OH vitamina D, fosfatasa alcalina, parathormona y magnesio, y se comparan con un grupo control de ancianos sin fractura de cadera. A los pacientes que, clínica y bioquímicamente, presentaban datos compatibles con probable osteomalacia se les realizaba una prueba terapéutica con vitamina D durante 6 meses, con posterior control analítico similar al descrito. Estudio comparativo con un nivel de significación de p < 0,05. Resultados: el 60% de los ancianos con fractura de cadera presentaba déficit de vitamina D al ingreso frente a un 9,5% en el grupo control (p = 0,004). Cinco pacientes presentaron probable osteomalacia; tras las pruebas terapéuticas 4 pacientes mejoraron su clínica y 3 normalizaron las concentraciones de fosfatasa alcalina. Conclusiones: el déficit de vitamina D es muy prevalente en la población anciana; en este estudio se asoció a fractura de cadera. La osteomalacia es una enfermedad curable que, pese a su baja prevalencia, debe sospecharse en estos casos

Objective: to determine the prevalence of vitamin D deficiency in elderly individuals with hip fracture compared with a control group of similar age, and to analyze its association with the risk of fracture. A secondary aim was to determine the relationship between vitamin D deficiency and suspected osteomalacia based on clinical and biochemical evidence. Material and methods: we performed a prospective descriptive study of 68 non-institutionalized elderly individuals with prior functional independence who were admitted to hospital with hip fracture. A clinical history was taken and blood samples for calcium, phosphorus, 25-OH vitamin D, alkaline phosphates, parathormone and magnesemia determinations were obtained. Patients with clinical and biochemical evidence compatible with osteomalacia underwent a therapeutic intervention consisting of vitamin D supplementation for 6 months and laboratory determinations similar to those described above were performed. A comparative study with a significance level of p < 0.05. Results: sixty percent of the elderly patients with hip fracture had vitamin D deficiency on admission to hospital versus 9.5% of the control group (p = 0.004%). Five patients had probable osteomalacia. After the therapeutic intervention, symptoms improved in four patients and alkaline phosphate levels were normalized in three. Conclusions: vitamin D deficiency is highly prevalent in the elderly population and is associated with a higher risk of hip fracture. Osteomalacia is a curable disease which, despite its low prevalence, should be considered in these patients

Hypophosphatemic rickets and osteomalacia.

The hypophosphatemic conditions that interfere in bone mineralization comprise many hereditary or acquired diseases, all of them sharing the same pathophysiologic mechanism: reduction in the phosphate reabsorption by the renal tubuli. This process leads to chronic hyperphosphaturia and hypophosphatemia, associated with inappropriately normal or low levels of calcitriol, causing osteomalacia or rickets in children and osteomalacia in adults. X-linked hypophosphatemic rickets, autosomal-dominant hypophosphatemic rickets, and tumor-induced osteomalacia are the main syndromes involved in the hypophosphatemic rickets. Although these conditions exhibit different etiologies, there is a common link among them: increased activity of a phosphaturic factor, being the fibroblast growth factor 23 (FGF-23) the most studied one and to which is attributed a central role in the pathophysiology of the hyperphosphaturic disturbances. Activating mutations of FGF-23 and inactivating mutations in the PHEX gene (a gene on the X chromosome that codes for a Zn-metaloendopeptidase proteolytic enzyme which regulates the phosphate) involved in the regulation of FGF-23 have been identified and have been implicated in the pathogenesis of these disturbances. Genetic studies tend to show that the phosphorus homeostasis depends on a complex osteo-renal metabolic axis, whose mechanisms of interaction have been poorly understood so far. This paper reviews the current knowledge status concerning the pathophysiology of phosphate metabolism regulation and the pathophysiologic basis of hypophosphatemic rickets. It also analyzes the clinical picture and the therapeutic aspects of these conditions as well.

Development of renal bone disease.

Renal osteodystrophy (ROD) develops as the early stages of chronic renal failure (CRF) and covers a spectrum of bone changes observed in the uraemic patient, which extend from high remodelling bone disease (frequently known as osteitis fibrosa) to low turnover, or adynamic disease. Between these two extremes there are also cases of bone mineralization compromised in variable degrees, as is the case of 'mixed bone disease' and osteomalacia. The dynamic process of bone remodelling is compromised in CRF, and a positive or negative bone balance can be observed in uraemic patients. In addition to the classic modulators of bone remodelling, like parathyroid hormone, calcitriol and calcitonin, other factors were recently identified as significant modulators of osteoblast and osteoclast activation in uraemic patients. In fact, different cytokines and growth factors, acting at an autocrine or paracrine level, seem to play a relevant role in the bone and mineral changes observed in uraemia. Recently, observations have been made of the development of more sensitive and specific techniques to assay different biochemical markers of bone turnover and mineral metabolism. Analogously, new contributions of conventional bone histology, bone immunocytochemistry and molecular biology, which enabled the understanding of some etiopathogenic mechanisms of ROD, were observed.

Hypophosphatemic rickets and osteomalacia / Raquitismo hipofosfatêmico e osteomalácia

The hypophosphatemic conditions that interfere in bone mineralization comprise many hereditary or acquired diseases, all of them sharing the same pathophysiologic mechanism: reduction in the phosphate reabsorption by the renal tubuli. This process leads to chronic hyperphosphaturia and hypophosphatemia, associated with inappropriately normal or low levels of calcitriol, causing osteomalacia or rickets in children and osteomalacia in adults. X-linked hypophosphatemic rickets, autosomal-dominant hypophosphatemic rickets, and tumor-induced osteomalacia are the main syndromes involved in the hypophosphatemic rickets. Although these conditions exhibit different etiologies, there is a common link among them: increased activity of a phosphaturic factor, being the fibroblast growth factor 23 (FGF-23) the most studied one and to which is attributed a central role in the pathophysiology of the hyperphosphaturic disturbances. Activating mutations of FGF-23 and inactivating mutations in the PHEX gene (a gene on the X chromosome that codes for a Zn-metaloendopeptidase proteolytic enzyme which regulates the phosphate) involved in the regulation of FGF-23 have been identified and have been implicated in the pathogenesis of these disturbances. Genetic studies tend to show that the phosphorus homeostasis depends on a complex osteo-renal metabolic axis, whose mechanisms of interaction have been poorly understood so far. This paper reviews the current knowledge status concerning the pathophysiology of phosphate metabolism regulation and the pathophysiologic basis of hypophosphatemic rickets. It also analyzes the clinical picture and the therapeutic aspects of these conditions as well.

Os distúrbios hipofosfatêmicos que comprometem a mineralização óssea englobam várias doenças, hereditárias e adquiridas, as quais compartilham um mesmo mecanismo fisiopatológico: a diminuição da reabsorção de fosfato nos túbulos renais. Este processo promove hiperfosfatúria e hipofosfatemia crônicas, associadas a níveis inapropriadamente normais ou baixos de 1,25 (OH)2D3, com conseqüente desordem do metabolismo ósteo-mineral, resultando em raquitismo e osteomalácia na faixa etária pediátrica e em osteomalácia nos adultos. O raquitismo hipofosfatêmico ligado ao X, o raquitismo hipofosfatêmico autossômico dominante e a osteomalácia induzida por tumor são as principais síndromes que constituem os raquitismos hipofosfatêmicos. Apesar de estas doenças apresentarem etiopatogenias distintas, as evidências bioquímico-moleculares indicam uma base fisiopatológica em comum: maior atividade de um agente fosfatúrico, sendo o fator de crescimento do fibroblasto 23 (FGF-23) o mais estudado e ao qual é atribuído um papel central na fisiopatologia destes distúrbios. Várias mutações ativadoras do gene do FGF-23 e mutações inativadoras do gene localizado no cromossomo X que codifica uma enzima proteolítica Zn-metaloendopeptidase reguladora do fosfato (PHEX), implicada na regulação do FGF-23, já foram identificadas, e sua participação reconhecida na gênese destes distúrbios. Os dados dos estudos genéticos nesta área convergem para a hipótese de que a homeostase do fósforo estaria vinculada a um complexo eixo metabólico ósteo-renal, cujos mecanismos de interação entre seus vários componentes têm sido aos poucos elucidados. Este artigo revisa o atual estado de conhecimento dos mecanismos fisiológicos envolvidos na regulação do metabolismo do fosfato, das bases fisiopatológicas dos raquitismos hipofosfatêmicos e analisa aspectos clínicos e de tratamento disponíveis para estas condições.

[Hyperparathyroidism associated with hypophosphatemic osteomalacia: case report and review of the literature]. / Hiperparatireoidismo associado à osteomalacia hipofosfatêmica do adulto: relato de caso e revisão da literatura.

Adult-onset hypophosphatemic osteomalacia is a rare disease characterized by hypophosphatemia, increased levels of alkaline phosphatase and decreased bone mass. Oral supplementation with phosphate and vitamin D is the main treatment and, in cases of oncogenic osteomalacia, tumor resection is mandatory. We report the case of a patient with hypophosphatemic osteomalacia of an unknown cause. Despite extensive search, no tumor was found. The patient was treated with phosphate for a long period and developed tertiary hyperparathyroidism. Serum PTH levels did not return to normal after surgical excision of three parathyroids and the patient refused to continue clinical investigation and treatment. After ten years absent from the hospital, during which medications were used irregularly, she was admitted with multiple fractures and respiratory insufficiency caused by severe thoracic deformities, and died. The authors discuss the relationship between osteomalacia and hyperparathyroidism and the aggressive course of the disease.