Effective Oral Treatment of Severe Paget's Disease of Bone With Apd (3‐amino‐i‐hydroxypropylidene‐1,1‐bisphosphonate); A Comparison With Combined Calcitonin + Ehdp (1 ‐hydroxyethylidene‐1,1 ‐bisphosphonate)

Abstract

Ten patients with severe Paget's disease of bone and serum alkaline phosphatase (sAP) greater than 900 IU/l were treated for six months with the oral diphosphonate APD, (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). By the end of the treatment period there was a reduction in the log mean urine hydroxyproline (uHP) and the log mean sAP of 92% and 87% respectively. In four patients both sAP and uHP fell to within the normal range and remained normal for at least six months after therapy was stopped. Bone scintigraphy showed a fall in 99mTc-MDP uptake in sites of active Paget's disease in all patients and histomorphometry showed no increase in osteoid. Repair of radiological osteolytic lesions was observed in 6/6 patients and progression of tibial osteolytic wedges was arrested in 5/5 patients and reversed in four. This improvement persisted six months after completion of therapy but further wedge progression occurred in one patient whose urine HP remained elevated. There were no serious effects though five patients complained of nausea. The clinical and biochemical responses to APD were equivalent to those observed in the same patients during a previous six month course of combined therapy with human calcitonin (CT) + EHDP except that there was additional biochemical and radiological evidence of bone healing. This study confirms PAD as an effective treatment of severe Paget's disease of bone.

Intravenous aminobisphosphonate in Paget's disease: clinical, biochemical, histomorphometric and radiological responses

“…It is noteworthy that, while all our patients responded biochemically and all those with radiographic lytic bone lesions demonstrated a positive response, few of the patients for whom biopsy information was available achieved normal-ization of histomorphometric indices (Fig. 3), despite some improvement in all indices in both the mild-moderate and severe groups . Fraser et al (1984) also found a lack of significant histomorphometric changes in six patients after APD therapy.…”

“…One of the newer bisphosphonates, 3-amino-1-hydroxypropylidene-I , I-bisphosphonic acid (APD) attaches to bone matrix and inhibits osteoclast activity both directly and by preventing recruitment and differentiation of precursor mononuclear cells (Boonekamp et al, 1986;Lowik et al, 1988). The use of APD in the treatment of Paget's disease permits bone turnover to be reduced to an average of 30% of pretreatment levels (Fraser et al, 1984;Adami et al, 1986;Harinck et al, 1987a. b).…”

Pamidronate is effective for paget's disease of bone refractory to conventional therapy

“…Indeed, etidronate has been shown to increase the fracture risks in these patients [19]. However, the newer generation of bisphosphonates such as pamidronate (clodronate and residronate), has been reported to improve healing of osteolytic lesions [12,14].…”

Optimal frequency of administration of pamidronate in patients with hypercalcaemia of malignancy

“…Bisphosphonates have been used successfully for the treatment of HM over the past few years (Fleisch, 1982;Fraser et al, 1984;Wimalawansa, 1993Wimalawansa, , 1994. In most countries, calcitonin and at least one of the parenterally administered bisphosphonates are now approved for the treatment of HM (Wimalawansa, 1989;1993).…”

“…In patients with severe hypercalcaemia in whom the plasma calcium level needs to be reduced rapidly, combined treatment with calcitonin and bisphosphonate is safe and highly effective (Fraser et al, 1984;Ralston et al. 1986;Wimalawansa, 1993).…”