Case report: Osteomalacia due to bisphosphonate treatment in a patient on hemodialysis.

BACKGROUND: No publications have reported on osteomalacia in patients receiving intermittent cyclical therapy with etidronate (a bisphosphonate) and undergoing long-term hemodialysis (HD). CASE PRESENTATION: We report on a 46-year-old Japanese man admitted to our hospital for further examination of left forearm pain. Maintenance HD was started at age 24 years, and the man had been on HD since then. At age 38 years, surgical parathyroidectomy was performed for secondary hyperparathyroidism; iliac crest bone biopsy performed at the same time showed osteitis fibrosa. The active vitamin D3 preparation calcitriol was started, and intermittent cyclical etidronate therapy was introduced 2 years later for osteoporosis. At age 45 years, the patient stopped taking calcitriol because of hypercalcemia but continued with etidronate. At age 46 years, a pseudofracture with a Looser zone occurred in the left ulna, and left femur bone biopsy revealed osteomalacia. Etidronate was discontinued, and calcitriol was restarted; open reduction and internal fixation with an angular stability plate were performed. Union of the bone was achieved 10 months after the operation. At age 49 years, a lumber bone biopsy confirmed improved bone morphometry. CONCLUSIONS: We believe that intermittent cyclical etidronate therapy without administration of active vitamin D3 during long-term HD might have induced osteomalacia, resulting in the ulna insufficiency fracture. Therefore, we propose that administration of active vitamin D3 is essential to prevent osteomalacia in patients on long-term HD who are receiving bisphosphonates and have potential vitamin D3 deficiency.

Brown tumor of the jaws as a manifestation of tertiary hyperparathyroidism: A literature review and case report.

Brown tumor of the jaws is a manifestation of hyperparathyroidism consisting of osteolytic lesions that show proliferation of multinucleated giant cells in the maxilla and/or mandible. Differential diagnosis of these lesions from local central giant-cell granuloma is mandatory for the correct treatment of the patient. Radiographic and histopathological exams of the jaw lesion are not sufficient to determine the diagnosis, which requires laboratory tests including serum levels of calcium, alkaline phosphatase, parathyroid hormone (PTH) and phosphate, and radiographic examination of other bones as well, such as hand-wrist, pelvis, and femur. We present here a brief literature review focusing on the clinical and radiographic features, diagnostic criteria and treatment of brown tumor and also report a case of the disease affecting the jaw.

A patient with a history of breast cancer and multiple bone lesions: a case report.

BACKGROUND: Long-term severe hyperparathyroidism leads to thinning of cortical bone and cystic bone defects referred to as osteitis fibrosa cystica. Cysts filled with hemosiderin deposits may appear colored as "brown tumors." Osteitis fibrosa cystica and brown tumors are occasionally visualized as multiple, potentially corticalis-disrupting bone lesions mimicking metastases by bone scintigraphy or 18F-fluorodeoxyglucose positron emission tomography. CASE PRESENTATION: We report a case of a 72-year-old white woman who presented with malaise, weight loss, and hypercalcemia. She had a history of breast cancer 7 years before. The practitioner, suspecting bone metastases, initiated bone scintigraphy, which showed multiple bone lesions, and referred her to our hospital for further investigations. Laboratory investigations confirmed hypercalcemia but revealed a constellation of primary hyperparathyroidism and not hypercalcemia of malignancy; in the latter condition, a suppressed rather than an increased value of parathyroid hormone would have been expected. A parathyroid adenoma was found and surgically removed. The patient's postoperative course showed a hungry bone syndrome, and brown tumors were suspected. With the background of a previous breast cancer and lytic, partly corticalis-disrupting bone lesions, there was a great concern not to miss a concomitant malignant disease. Biopsies were not diagnostic for either malignancy or brown tumor. Six months after the patient's neck surgery, imaging showed healing of the bone lesions, and bone metastases could be excluded. CONCLUSIONS: This case shows essential differential diagnosis in a patient with hypercalcemia and multiple bone lesions. Whenever multiple, fluorodeoxyglucose-avid bone lesions are found, malignancy and metabolic bone disease should both be included in the differential diagnosis. Fluorodeoxyglucose-avid and corticalis-disrupting lytic lesions also occur in benign bone disease. There may be very few similar cases with heterogeneous and widespread bone lesions reported in the literature, but we think our patient's case is particularly remarkable for its detailed imaging and the well-documented course.

Brown tumours of the tibia and second metacarpal bone in a woman with severe vitamin D deficiency.

Brown tumours caused by vitamin D deficiency are rare. Most cases are caused by primary hyperparathyroidism, and are rarely caused by secondary hyperparathyroidism in cases of renal failure. We present a case of Brown tumours of the tibia and second metacarpal bone in a 50-year-old woman who had a low dietary intake of vitamin D and had worn a veil for most of her adult life. The Brown tumours were caused by vitamin D deficiency and secondary hyperparathyroidism. The patient improved on treatment with vitamin D3 and calcium supplements. This is a rare case and the first, to our knowledge, with a Brown tumour of the tibia caused by vitamin D deficiency due to decreased dietary intake and decreased exposure to sunlight. The course of treatment and investigations of the patient are described.

[Radiographic healing of sarcoid bone erosion]. / Radiologische Heilung einer Erosion bei Knochensarkoidose.

Sarcoidosis is a systemic granulomatous disease that primarily affects the lung and other organs. Patients with dactylitis should be screened for abnormalities of the skin, eyes and lungs. Even in patients with normal-range ACE sarcoidosis could be confirmed by tissue biopsy. Treatment with methotrexate and steroids can relieve symptoms and stabilize the disease. In refractory cases leflunomide, azathioprine, hydroxychloroquine or antibodies against TNF-alpha can be additionally administered.

[Parathyroid and bone. Calcimimetics and bone metabolism].

Calcimimetics suppress parathyroid hormone (PTH) secretion by allosterically acting on parathyroid calcium-sensing receptor. It has been already shown that one of calcimimetics decreases PTH level, calcium-phosphate product and bone-specific alkaline phosphatase (BAP) in patients with secondary hyperparathyroidism (SHPT) caused by end-stage renal disease. It has been also described that this drug ameliorates osteitis fibrosa in uremic rats. However, there has been so far insufficient evidence showing that calcimimetics increase bone mineral density and decrease fractures in human. Effects of calcimimetics on bone metabolism need to be investigated by clinical studies for longer usage of this drug in the future.

Regression of skeletal manifestations of hyperparathyroidism with oral vitamin D.

CONTEXT: Parathyroidectomy is the only effective therapy for osteitis fibrosa cystica in hyperparathyroidism. OBJECTIVE: The objective of this study was to describe the changes of skeletal and nonskeletal manifestations in a patient with hyperparathyroidism and renal failure after oral vitamin D therapy. DESIGN: This was a descriptive case report. SETTING: The patient was followed up in a referral center. PATIENT: A 55-yr-old male patient with moderate renal failure was referred for expansile lytic lesions affecting several ribs and the spinous process of T12. His creatinine was 1.8 mg/dl; calcium, 8.9 mg/dl; PTH, 666 pg/ml; and 1,25 dihydroxy-vitamin D, 27 pg/ml. Bone mineral density (BMD) Z-scores by dual-energy x-ray absorptiometry were -4.1 at the spine, -1.7 at the hip, and -4.3 at the forearm. MAIN OUTCOME MEASURES: The main outcome measures were the skeletal manifestations of hyperparathyroidism. RESULTS: At 10 months of therapy, calcium level was 10 mg/d, PTH level declined to 71 pg/ml, and BMD increased by 12% at the spine and 18% at the hip. Computerized tomography (CT) cuts revealed marked regression in the lytic lesions. At 2 yr, BMD increased by an additional 6% at the spine, and there were no further changes in the lytic lesions by CT. The vitamin D receptor genotype using the restriction enzymes Bsm1, Taq1, and Apa1 was Bb, tt, and AA. CONCLUSIONS: We showed regression of severe skeletal abnormalities of hyperparathyroidism documented by serial CT images in response to oral vitamin D therapy. It is possible that the vitamin D receptor genotype of the patient modulated this response.

Highly aggressive brown tumor in the jaw associated with tertiary hyperparathyroidism.

The purpose of this paper is to describe the case of a 12-year-old patient with end-stage chronic renal failure. The patient presented with an osteolytic lesion in the mandible with expansion of the buccal, lingual, and occlusal cortical bone, as well as dislocation of the teeth in the area. The calcium, creatinine, and parathormone (PTH) contents of the blood were elevated. A histopathological examination of the jaw lesion revealed the presence of a brown tumor lesion, which is associated with hyperparathyroidism (HPT). An adenoma was found in the upper left parathyroid, a finding compatible with the diagnosis of tertiary HPT. In spite of the continuous ambulatory peritoneal dialysis instituted, the osteolytic lesion kept on growing. A conservative treatment employing an association of intralesional corticosteroid and salmon calcitonin (inhaled) was carried out. After 14 months of therapy, a reduction in size and complete calcification of the lesion were achieved. Aesthetic osteoplasty of the jaw was then performed.

Tumores pardos: Dignóstico indirecto en pacientes paratiroidectomizados / Brown Tumors: Indirect diagnostic in parathiroidectomyzed patients

La principal causa de hiperparatiroidismo (HPT) secundario es la insuficiencia renal terminal, que frecuentemente precisa de cirugía para suc orrección. Tras esta cirugía aparece el síndrome de hueso hambriento, por el que aumentan las necesidades de calcio (Ca) y fósforo (P) en el organismo. Estas necesidades pueden preverse según los niveles de fosfatasa alcalina (FA) previos a la cirugía. En determinadas circunstancias, las necesidades reales exceden a las teóricas. Planteamos considerar como una de las posibles causas de esta mayor necesidad la existencia de tumores pardos. Aportamos dos casos que justifican esta pretensión

The main cause of secondary hyperparathyriodismis end-stage renal disease, that requires surgical correction in many cases. Hungry Bone Syndrome following parathyroidectomy can be recognized by hypocalcemia, that requires (extra) calcium and phosphorus administration. Serum alkaline phosphatase level before surgery is a good predictor of right quantity of calcium and phosphorus nedeed. However, real needs somethimes exceed theoretical ones. We consider brown tumor as one of fue possible reasons for this gap. We report cases which support it

Hammers and nails: a report.

A case report where parathyroid bone disease simulates bone metastases. Subsequent treatment of underlying hyperparathyroidism causes a marked improvement in bone disease, leading to a review of the initial diagnosis.

Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure.

Osteitis fibrosa, a frequent complication of chronic renal failure, is characterized by increased rates of bone formation and bone resorption due to increased secretion of parathyroid hormone (PTH). Effective treatment with oral calcitriol is often impossible in patients with osteitis fibrosa, because low doses may cause hypercalcemia. Because short-term infusions of intravenous calcitriol are capable of suppressing the secretion of parathyroid hormone in patients with uremia without causing hypercalcemia, we evaluated the effectiveness of long-term intermittent calcitriol infusions (1.0 to 2.5 micrograms three times weekly, during dialysis) in treating severe osteitis fibrosa in 12 consecutive patients on hemodialysis whose disease was refractory to conventional therapy. After a mean (+/- SE) treatment period of 11.5 +/- 1.4 months, the mean bone-formation rate declined from 1642 +/- 277 to 676 +/- 106 microns 2 per square millimeter per day (P less than 0.01) in the 11 patients who successfully completed the study. Similar reductions occurred in the osteoblastic osteoid (18 +/- 3 to 9 +/- 2 percent; P less than 0.01) and the degree of marrow fibrosis (6.2 +/- 1.7 to 3.5 +/- 1.3 percent; P = 0.01). Concomitant serum biochemical changes included increased calcium levels (2.55 +/- 0.03 to 2.67 +/- 0.05 mmol per liter; P less than 0.01), decreased alkaline phosphatase levels (489 +/- 77 to 184 +/- 32 U per liter; P less than 0.001), and decreased levels of PTH (amino-terminal, 172 +/- 34 to 69 +/- 16 ng per liter in five patients, P less than 0.03; and carboxy-terminal, 1468 +/- 467 to 1083 +/- 402 ml-eq per liter in six patients, P not significant). Although the majority of the patients had transient episodes of asymptomatic hypercalcemia, this complication could be quickly reversed by temporarily halting treatment or decreasing the dose of calcitriol. We conclude that long-term intermittent infusions of intravenous calcitriol are effective in ameliorating osteitis fibrosa in patients on dialysis. Patients whose osteitis fibrosa is refractory to oral calcitriol and who are candidates for parathyroidectomy should be considered first for intravenous calcitriol therapy.

Marked direct suppression of primary hyperparathyroidism with osteitis fibrosa cystica by intravenous administration of 1,25-dihydroxycholecalciferol.

A marked direct suppression of primary hyperparathyroidism with osteitis fibrosa cystica has been achieved by the intravenous administration of 1,25-dihydroxycholecalciferol [1,25(OH)2D]. In a recent survey of 306 patients with primary hyperparathyroidism (PHPT), we hypothesized that the far higher degree of parathyroid hormone (PTH) hypersecretion in PHPT with osteitis fibrosa cystica than in PHPT without overt bone disease might be due to the absence of suppression of hormonal hypersecretion by the low-to-normal circulating 1,25(OH)2D reflecting a relative vitamin D deficiency. To test this hypothesis, a patient having hypercalcemic PHPT with florid osteitis fibrosa cystica and normal serum 1,25(OH)2D was given increasing daily doses of intravenous calcitriol (0.5-2 micrograms) for several days. Doubling the level of circulating 1,25(OH)2D from 48 to 100-114 pg/ml was accompanied by a marked decline (46%) in serum iPTH(1-84), without a change in the serum calcium concentration. A lowered set point of parathyroid cells for calcium, and a diminished maximum secretory rate of PTH, may contribute to the marked suppression of PHPT.

Management of bone disease in the dialysis patient.

Bone disease arises in dialysis patients from either secondary hyperparathyroidism or aluminum accumulation. Certain clinical features and biochemical characteristics may help distinguish these disorders, although a bone biopsy is required for a definitive diagnosis. Hyperparathyroidism is managed by correcting serum phosphorus (dietary phosphate restriction plus phosphate binding agents), raising serum calcium (appropriate dialysate Ca, oral Ca supplements, and vitamin D sterols), and by the direct effect of vitamin D on the parathyroid glands. When these fail, parathyroidectomy is necessary. Aluminum-related bone disease is prevented by eliminating aluminum from dialysate and minimizing the intake of aluminum-containing gels. Preexisting aluminum intoxication can be treated with repeated infusions of desferrioxamine.