The Cardiovascular System in Paget's Disease of Bone and the Response to Therapy with Calcitonin and Diphosphonate

Abstract

Summary: The cardiovascular system in Paget's disease of bone and the response to therapy withcalcitonin and diphosphonate. J. W. Henley, R. S. Croxson and H. K. Ibbertson, Aust. N.Z. J. Med., 1979, 9, pp. 390–397. The cardiovascular status of 39 patients with Paget's disease of bone was studied before and after treatment with porcine calcitonin or diphosphonate (disodium etidronate). Cardiovascular abnormalities were detected in 32 patients. Systemic hypertension was present in four, ischaemic heart disease in five, cardiac enlargement in ten and evidence of valvular and/or arterial calcification in 14. Before treatment the cardiac index was elevated in 27 of 39 patients (69%) and there was a significant direct correlation with the serum alkaline phosphatase (r = 0·68, P < 0·001), urine total hydroxyproline (r = 0·51, P<0·001) and percentage skeletal involvement (r = 0·51, P<0·001). After 24 weeks' treatment with either diphosphonate or calcitonin, there was a fall in cardiac index in 17 of 18 patients; the mean reduction being 12·7% for the calcitonin group and 27% for the diphosphonate treated patients. There was a rise in mean arterial pressure and peripheral resistance in both groups (P< 0·025) and a fall in cardiothoracic ratio (P<0·005) but no change in heart rate. In 17 patients studied 24 weeks after the end of therapy, similar, though less marked changes were observed. The cardiac index was lower than the pretreatment value in all eight diphosphonate treated patients but cardiac index and biochemical indices were higher than basal levels in three of nine patients who had received calcitonin. This study confirms a high incidence of cardiovascular complications and an increased cardiac output in most patients with moderate or severe Paget's disease of bone. There was a significant correlation between these abnormalities, the biochemical indices of disease activity and the radiological evidence of skeletal disease. Treatment with either diphosphonate or calcitonin caused partial or complete biochemical remission and a reduction in cardiac index in most patients studied.

High output cardiac failure

“…The use of the calcitonin and the diphosphonate has attained the most widespread acceptance, but mithramycin, and the combination of thiazide diuretics and calcium supplements are still used but are less adequately evaluated [48]. The cardiovascular effects of Paget's disease have been shown to respond rapidly to treatment with calcitonin and more slowly with diphosphonate [32,48].…”

“…The increased cardiac output is presumably related to multiple, small systemic arteriovenous fistulae in the bones involved by these disorders, which lower peripheral resistance [32][33][34]. The increased cardiac output is proportional to the amount of skeletal involvement.…”

Dental, Visual, Auditory and Olfactory Complications in Paget's Disease of Bone

“…Cardiovascular, 34–36 arthritic, 37–39 and neoplastic 40,41 problems have been reported previously in patients with Paget's disease. We observed that the Paget's population reported a greater percentage of arthritic and osteoporotic problems than did the controls.…”

Paget's Disease of Bone

“…Bony hypervascularity, present to some extent in all patients with Paget's disease, is believed to cause the warmth of the skin overlying bone in many patients. With extensive skeletal involvement cardiac output is increased; this can lead to high‐output heart failure or, more commonly, to exacerbation of any underlying congestive heart failure or ischemic heart disease 24 …”

“…The calcitonins, because of their rapidity of action, are most appropriate for patients with severe symptoms who need rapid relef? 26–29 Treatment is usually continued for rune to 12 months, and additional courses are often given for symptomatic relapses. Most patients experience symptomatic relief from calcitonin therapy after two to eight weeks, and dramatic improvements in neurologic and cardiovascular complications have been reported 19,20,24,32 . Effects on biochemical determinations usually reach a plateau after six to eight weeks of therapy; most patients achieve about 50 per cent reductions of pretreatment abnormalities.…”