The long-term skeletal effects of EHDP in dogs

Flora, L.; Hassing, Gordon S.; Cloyd, G.G.; Bevan, J A; Parfitt, A. M.; Villanueva, A. R.

doi:10.1016/0221-8747(81)90045-x

Cited by 87 publications

(32 citation statements)

References 16 publications

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“…Moreover, animal studies suggest that three to ®ve times higher dosages are needed to induce such complications compared to the dosages currently used in SCI patients. 151 The main reasons for patients to discontinue EHDP treatment are gastro-intestinal symptoms such as nausea, diarrhoea, and abdominal distress.…”

Section: Disodium Etidronate (Ehdp)mentioning

confidence: 99%

Neurogenic heterotopic ossification in spinal cord injury

2002

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Neurogenic heterotopic ossi®cation (NHO) is a frequent complication in spinal cord injury (SCI) that is often di cult to treat. This review emphasizes the incidence, risk factors and clinical signs of NHO in SCI patients. Although the exact pathophysiology underlying NHO in neurologic patients is not yet understood, di erent pathogenic mechanisms have been proposed in the literature. A selection of the most important theories will be given and discussed. Moreover the di erent diagnostic, therapeutic, and preventive methods currently used in NHO management after SCI will be reviewed.

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Section: Disodium Etidronate (Ehdp)mentioning

confidence: 99%

Neurogenic heterotopic ossification in spinal cord injury

2002

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“…High doses in animals are associated with increased microdamage 134,135 and even fractures. 136 It has been suggested that bisphosphonates might prevent naturally occurring microscopic cracks in bone from healing. There have been isolated reports of adynamic bone associated with bisphosphonate usage, 137 but long-term use of the bisphosphonates in the therapy of osteoporosis seems to be safe.…”

Section: Some Current Issues With Bisphosphonates: Bone Architecturementioning

confidence: 99%

Bisphosphonates: Mode of Action and Pharmacology

2007

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The profound effects of the bisphosphonates on calcium metabolism were discovered over 30 years ago, and they are now well established as the major drugs used for the treatment of bone diseases associated with excessive resorption. Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in pediatric bone diseases, notably osteogenesis imperfecta. Bisphosphonates are structural analogues of inorganic pyrophosphate but are resistant to enzymatic and chemical breakdown. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts where they interfere with various biochemical processes. The simpler, non-nitrogen-containing bisphosphonates (eg, clodronate and etidronate) can be metabolically incorporated into nonhydrolysable analogues of adenosine triphosphate (ATP) that may inhibit ATP-dependent intracellular enzymes. In contrast, the more potent, nitrogen-containing bisphosphonates (eg, pamidronate, alendronate, risedronate, ibandronate, and zoledronate) inhibit a key enzyme, farnesyl pyrophosphate synthase, in the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small guanosine triphosphate (GTP)-binding proteins (which are also GTPases) such as Rab, Rho, and Rac. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explains the loss of osteoclast activity. The recently elucidated crystal structure of farnesyl diphosphate reveals how bisphosphonates bind to and inhibit at the active site via their critical nitrogen atoms. Although bisphosphonates are now established as an important class of drugs for the treatment of many bone diseases, there is new knowledge about how they work and the subtle but potentially important differences that exist between individual bisphosphonates. Understanding these may help to explain differences in potency, onset and duration of action, and clinical effectiveness.www.pediatrics.org/cgi

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“…28,29 The experiments in animals con®rm these clinical observations. Flora et al reported that higher doses of etidronate can be administered in patients without fear of a fracture problem; 30 their results obtained in adult beagle dogs showed that spontaneous bone fractures develop only when the dose of etidronate was approximately 3 ± 5 times the dose of 20 mg/kg/day used in our study.…”

Section: Discussionmentioning

confidence: 41%

Evaluation and management of heterotopic ossification in patients with spinal cord injury

Banovac

Gonzalez

1997

Spinal Cord

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Sixty-three patients with paralysis secondary to spinal cord injury (SCI) were screened for heterotopic ossi®cation (HO) by bone scintigraphy 27+14 (mean+SD) days after SCI. There were four female and 59 male patients, 36 had paraplegia and 27 tetraplegia. The age of patients was 28+9 years. Bone scintigraphy was obtained with a 3-phase test using 99m-technetium labeled diphosphonate, and the positive third phase was used as a criterion for diagnosis of HO. Bone scintigraphy was negative for HO in 27 patients (14 tetraplegic and 13 paraplegic) and positive in 36 patients (13 tetraplegic and 23 paraplegic). The patients with positive HO were treated with etidronate, ®rst with an intravenous dose of 300 mg/day for 3 days, and then with an oral dose of 20 mg/kg/day for 6 months. The follow-up of patients consisted of clinical and radiographic evaluations every 2 ± 4 months. The extent of HO was classi®ed radiographically. In the treated group of patients who completed the entire course of etidronate therapy one patient developed HO, the remaining 28 (97%) patients had no radiographic evidence of HO during the follow-up of 10.6+4.5 months after initiation of therapy.Our data indicate that: (a) early HO can be detected in the asymptomatic patients using bone scintigraphy on the average of 4 weeks (27+14 days) after SCI and (b) the therapy with etidronate might be e ective in the prevention of HO in majority of patients when the treatment is initiated in an early stage of heterotopic bone formation.

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The long-term skeletal effects of EHDP in dogs

Cited by 87 publications

References 16 publications

Neurogenic heterotopic ossification in spinal cord injury

Neurogenic heterotopic ossification in spinal cord injury

Bisphosphonates: Mode of Action and Pharmacology

Evaluation and management of heterotopic ossification in patients with spinal cord injury

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