Effects of a New Aminodiphosphonate (Aminohydroxybutylidene Diphosphonate) in Patients With Osteolytic Lesions From Metastases and Myelomatosis

Attardo-Parrinello, Giuseppe; Merlini, Giampaolo; Pavesi, Franco; Crema, Francesca; Fiorentini, M; Ascari, E

doi:10.1001/archinte.1987.00370090105018

Cited by 40 publications

(3 citation statements)

References 24 publications

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“…Many enzymes serve as catalysts along this multistep pathway and its various branches, and several inhibitor drugs target some of these enzymes, including the group of bisphosphonates, which inhibit farnesyl diphosphate synthase, usually prescribed to prevent bone resorption [1]. Alendronate is a second-generation nitrogen-containing bisphosphonate used for the treatment of metabolic bone disorders, osteoporosis, and Paget’s disease [2,3]. A rare hereditary autoinflammatory disorder, involving the second enzyme in the mevalonate/cholesterol pathway, is mevalonate kinase deficiency (MKD), caused by mutations in the MVK gene encoding the enzyme mevalonate kinase [4].…”

Section: Introductionmentioning

confidence: 99%

Weekly oral alendronate in mevalonate kinase deficiency

Cantarini

Vitale

Magnotti

et al. 2013

Orphanet J Rare Dis

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BackgroundMevalonate kinase deficiency (MKD) is caused by mutations in the MVK gene, encoding the second enzyme of mevalonate pathway, which results in subsequent shortage of downstream compounds, and starts in childhood with febrile attacks, skin, joint, and gastrointestinal symptoms, sometimes induced by vaccinations.MethodsFor a history of early-onset corticosteroid-induced reduction of bone mineral density in a 14-year-old boy with MKD, who also had presented three bone fractures, we administered weekly oral alendronate, a drug widely used in the management of osteoporosis and other high bone turnover diseases, which blocks mevalonate and halts the prenylation process.ResultsAll of the patient’s MKD clinical and laboratory abnormalities were resolved after starting alendronate treatment.ConclusionsThis observation appears enigmatic, since alendronate should reinforce the metabolic block characterizing MKD, but is crucial because of the ultimate improvement shown by this patient. The anti-inflammatory properties of bisphosphonates are a new question for debate among physicians across various specialties, and requires further biochemical and clinical investigation.

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Section: Introductionmentioning

confidence: 99%

Weekly oral alendronate in mevalonate kinase deficiency

Cantarini

Vitale

Magnotti

et al. 2013

Orphanet J Rare Dis

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“…In fact, the urinary Hyp excretion of the patient remained high after bisphosphonate therapy and did not correlate with serum levels of Ca and PTHrP, suggesting the possibility of increased osteoclastic bone resorption and depressed osteoblastic activity [30], since the alteration of Hyp in urine reflects the altered collagen metabolism associated with bone disease [15]. On the other hand, elevated urinary Hyp levels in patients with LOH [2] and primary hyperparathyroidism [1] were reported to be reduced to normal levels, correlating with Ca levels after the treatment with disphosphonate or bisphosphonate. The response of Hyp to bisphosphonate in our case implicated the involvement of different mechanisms between HHM produced by PTHrP and other types of hypercalcemia in the production of hypercalcemia.…”

Section: Discussionmentioning

confidence: 91%

Hypercalcemia associated with parathyroid hormone-related protein produced by B-cell type primary malignant lymphoma of the kidney

Shima

Maeda

et al. 1998

Annals of Hematology

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A patient with primary non-Hodgkin's (B-cell type) lymphoma of the kidney developed hypercalcemia at the terminal stage of the disease. Although the plasma parathyroid hormone level was low, urinary cyclic AMP excretion was elevated. Serum osteocalcin (BGP) was suppressed and the plasma level of 1,25(OH)2D was within the normal range. Serum concentrations of PTH-related protein (PTHrP)-like immunoreactivity (PRP-LI) were elevated, and the tissue concentration of PRP-LI in the postmortem lymph node showed high level along with elevated serum PRP-LI, furthermore the production of PTHrP by the tumor was demonstrated by immunohistochemistry and Northern blotting analysis. These findings indicate that the hypercalcemia of the patient was caused by the PTHrP-producing B-cell lymphoma. Hypercalcemia was restored to normocalcemia by bisphosphonate treatment. Our case will add further information on humoral hypercalcemia in B-cell lymphoma, which rarely has been demonstrated to produce PTHrP.

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“…Osteoclasts are required for at least some tumours to grow and destroy bone (Clohisy and Ramnaraine 1998). Consequently, drugs that inhibit the function of osteoclasts, such as bisphosphonates (Lin 1996), are used in human beings to inhibit tumour‐induced osteolysis, particularly from metastatic bone neoplasia arising from breast cancer or multiple myeloma (Attardo‐Parrinello and others 1987, Diener 1996, Mundy and Yoneda 1998). However, the effect of bisphosphonate drugs on primary bone neoplasia has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Use of the bisphosphonate drug alendronate for palliative management of osteosarcoma in two dogs

et al. 2000

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The bisphosphonate drug alendronate was used to suppress bone remodelling and tumour osteolysis as a palliative treatment for two dogs with osteosarcoma, one of the tibia and one of the maxilla. A spiral fracture associated with the tibial tumour healed after it was stabilised with an external skeletal fixator. Both dogs remained comfortable and survived for 12 and 10 months respectively after diagnosis, despite the fact that neither primary tumour was resected.

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Effects of a New Aminodiphosphonate (Aminohydroxybutylidene Diphosphonate) in Patients With Osteolytic Lesions From Metastases and Myelomatosis

Cited by 40 publications

References 24 publications

Weekly oral alendronate in mevalonate kinase deficiency

Weekly oral alendronate in mevalonate kinase deficiency

Hypercalcemia associated with parathyroid hormone-related protein produced by B-cell type primary malignant lymphoma of the kidney

Use of the bisphosphonate drug alendronate for palliative management of osteosarcoma in two dogs

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