Effect of daily etidronate on the osteolysis of multiple myeloma.

Abstract

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.

Use of Bisphosphonates in Skeletal Metastasis

“…The effectiveness of bisphosphonates has been evaluated by their ability to reduce skeletal events: (1) new bone lesions (x-rays or scintigraphy) ; (2) fractures (radiologic or clinical examination) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20); (3) bone pain (analgesics, visual analogue scale, pain score, requirement of irradiation or isotope therapy) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41); (4) performance status (Karnofsky, Zubrod, ECOG) (11 -20, 31-41); (5) quality of life measures (16-20, 36, 37, 40, 41); (6) hypercalcemia (11 -21, 25, 31 -38); (7) measurements of different bone markers (11 -13, 20, 28, 30, 35 -38, 40 -44); and (8) survival (11 -13, 15, 18 -20, 34 -38, 40, 41). Study endpoints have been defined as a reduction of skeletal events and complications as well as an improvement of quality of life and pain relief.…”

Bisphosphonates - Mechanisms of Action in Multiple Myeloma

“…Etidronate is a low potency bisphosphonate that appears to be of little bene® t in patients with multiple myeloma (22,23). Longterm use of etidronate is known to impair bone mineralization (6), and it seems unlikely that etidronate treatment would be of value in treating the bone disease associated with multiple myeloma.…”

The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma

“…39 Oral clodronate, and intravenous pamidronate and zoledronic acid have been found to reduce SREs in randomized clinical trials (Table 1). [40][41][42][43][44][45][46][47][48][49][50][51][52] Nevertheless, zoledronic acid is currently the most commonly used bisphosphonate because it is more potent than pamidronate in reducing bone resorption, it may prolong survival in a subset of MM patients and is very convenient in its administration. 51 However, despite the beneficial effect on SREs, bisphosphonates reduce only osteoclast activity without interfering with osteoblast bone formation.…”