Spontaneous Fractures of Uninvolved Bones in Patients with Paget??s Disease During Unduly Prolonged Treatment with Disodium Etidronate (EHDP)

Mautalén, C.; Gonzalez, Diana; El, Blumenfeld; E, Santini Araujo; Schajowicz, Fritz

doi:10.1097/00003086-198606000-00028

Cited by 22 publications

(4 citation statements)

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“…When used in high doses, even for 1 month, bone biopsies have shown evidence of osteoid accumulation and mineralization defects (Gibbs et al, 1986). Several reports of osteomalacia and fractures have been published (Boyce et al, 1984;Khairi et al, 1977;Mautalen et al, 1966). Therefore, treatment is limited to 6 month intervals.…”

Section: Clinical Usesmentioning

confidence: 99%

Journal of Bone and Mineral Research

Ott

1993

Journal of Bone and Mineral Research

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The bisphosphonates are analogs of naturally occurring pyrophosphate. They appear to block bone resorption much more than mineralization. A series of compounds has been investigated. These have antiresorptive potencies ranging from 1 to 10,000. So far, structure-function relationships have eluded definition. These drugs increase the bone density in women with postmenopausal osteoporosis by about 5%-10% over 1 year. The bone density then appears to plateau, but most studies are of short duration. Improved bone density does not necessarily result in stronger bone, but no studies have had adequate power to assess fracture incidence. Bone formation rates decrease as measured histomorphometrically. This occurs while the bone density is improving, which implies an inhibition of bone resorption that is probably due to direct toxicity to the osteoclasts. Etidronate blocks mineralization as well as resorption and can cause osteomalacia, which is not seen with low-dose cyclical etidronate or with the second-generation compounds. The long-term effects of interfering with the remodeling cycle are still not known. Subtle side effects may be those on the bone itself. These might go undetected, since bone pain or fractures usually are attributable to the underlying disease.

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Section: Clinical Usesmentioning

confidence: 99%

Journal of Bone and Mineral Research

Ott

1993

Journal of Bone and Mineral Research

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“…Although isolated reports of osteomalacic changes in the treatment of Paget's disease and osteopetrotic-like changes in the treatment of osteogenesis imperfecta have been published [19], most attention has been focused on concerns of potential altered or suppressed bone turnover. Al-Muderis et al reported unusual metaphyseal banding termed "zebra lines" in children treated with cyclical pamidronate for a wide range of pediatric osteopenic disorders [20].…”

Section: Discussionmentioning

confidence: 99%

Osteoclast abnormalities in fractured bone during bisphosphonate treatment for osteoporosis: a case report

2012

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Bisphosphonates have been widely used in the treatment of an array of bone disorders. Recent complications have included unusual femoral fractures in patients who have received long term bisphosphonate treatment for osteoporosis. Although it has been shown that bisphosphonates are effective by blunting osteoclast resorption, there has been little morphologic description of the local tissue activity at the site of these unusual fractures. To evaluate for local changes to bone morphology at the fracture site in patients presenting with a bisphosphonate-related femur fracture, a sample of cortical bone was obtained at the site of a bisphosphonate fracture and was processed in a nondecalcified manner. The specimen was evaluated for potential cellular changes consistent with bisphosphonate treatment. Significant osteoclast abnormalities at the fracture site were found in a 69-year-old woman treated for 2 years with Fosamax substantiating that bone remodeling at this site is distinctly abnormal. Addressing the osteoclast dysfunction should be a focus of future therapeutic attention and intervention.

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“…Nevertheless, normalization of ALP is not always possible in patients with a very extensive or active disease (15–17) even with a very high dose of bisphosphonates as was shown by Cundy et al who used intravenous pamidronate (18) . However, since bisphosphonates have a very long half life in bone (19) and high doses of some bisphosphonates may impair normal mineralization of bone, (20,21) it would be desirable for the shortest exposure to the drug to induce complete remissions.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Therapy with Oral Olpadronate in Active Paget's Disease of Bone

González¹,

Mautalén²

1999

Journal of Bone and Mineral Research

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One of the aims of the treatment of Paget's disease with bisphosphonates should be the normalization of the activity of the disease with the shortest possible exposure to the drug. Olpadronate (OPD) is a new bisphosphonate characterized by the dimethylation of the amino group, its potency is near to alendronate, and more soluble in the digestive media than other aminobisphosphonates. We treated 46 patients (28 men and 18 women, mean age 70 years) with active Paget's disease with oral OPD, 200 mg/day for 12 ± 2 days, except 2 patients who received 400 mg/day. Eight patients had never been treated before, and 38 had previously received antiosteolytic drugs. The period without treatment prior to OPD was (X ± 1 SD) 14 ± 12 months. Baseline bone alkaline phosphatase (BALP) (levels fell from (X ± 1 SD) 54.0 ± 62.7 IU/ml (range 22-396) to a lowest mean value of 16.2 ± 6.4 IU/ml (range 8-45) (normal range 5-21 IU/ml). Forty patients normalized BALP values, in most of the cases within the first 3 months after OPD treatment. Two patients showed partial response (> 50% decrease from baseline), three patients presented poor response (< 50% decrease from baseline), and one patient did not respond at all. Two patients complained of gastric discomfort, and one patient had diarrhea, which disappeared after discontinuation of the drug. Follow-up was carried out on 36 patients; 22 patients are still in remission, with an average length of 9.0 ± 2.6 months. Fourteen patients experienced relapse after 9 ± 2 months remission. In conclusion, a 12-day treatment with 200 mg/day of OPD proved to be a very effective and well tolerated therapy of Paget's disease and induced biochemical remissions in the vast majority of patients, even in those with very active

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Spontaneous Fractures of Uninvolved Bones in Patients with Paget??s Disease During Unduly Prolonged Treatment with Disodium Etidronate (EHDP)

Cited by 22 publications

References 0 publications

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Osteoclast abnormalities in fractured bone during bisphosphonate treatment for osteoporosis: a case report

Short-Term Therapy with Oral Olpadronate in Active Paget's Disease of Bone

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