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.

Effect of cyclical intermittent etidronate therapy on circulating osteoprotegerin levels in patients with rheumatoid arthritis

OBJECTIVE: To evaluate the role of serum osteoprotegerin (OPG) as a biochemical marker for disease activity assessment and drug monitoring in patients with rheumatoid arthritis (RA) treated with cyclical etidronate. DESIGN: Forty patients (35 women and 5 men) with RA of <5 years duration were randomized to receive intermittent cyclical etidronate therapy in conjunction with anti-rheumatic therapy or anti-rheumatic therapy alone (without etidronate) in a 2-year, open-label protocol. METHODS: Radiographs of hands and feet and serum samples for the determination of OPG, amino terminal propeptide (PINP), cross-linked C-telopeptide (ICTP) and amino terminal telopeptid of type I collagen were obtained at baseline and at 24 months. RESULTS: Etidronate treatment had no effect on circulating OPG levels, although the significant decline in PINP and ICTP (P=0.001 and P=0.04 respectively) reflected the efficacy of the anti-resorptive therapy. At baseline and at study termination, serum OPG correlated significantly with age (r=0.45; P=0.003 and r=0.56; P=0.0002 respectively). OPG was not related to biochemical markers of bone metabolism, indices of disease activity or radiographic disease progression. At baseline, the mean serum OPG was higher in patients receiving 5-10 mg/day prednisone (82.8+/-4.0 pg/ml, n=16) compared with those receiving <5 mg/day or with no prednisone (69.7+/-4.7 pg/ml, n=23) (P=0.05). CONCLUSIONS: Our results suggested that serum OPG measurement, perhaps because of the complexity of the regulation of the OPG, may be difficult to utilize in the evaluation of anti-resorptive therapy. Moreover, low dose corticosteroid-associated osteoporosis is probably not mediated by inhibition of OPG.