Quantitative Ultrasound of Bone and Markers of Bone Turnover in Cushing's Syndrome

Abstract

Quantitative ultrasound (QUS) of bone is a valuable tool in the assessment of postmenopausal osteoporosis. QUS and new markers of bone turnover have been poorly assessed in Cushing's syndrome, however. Twenty-five patients with Cushing's syndrome (20 women, 3 men; mean age +/- SEM: 38+/-2 years) were studied and compared with 35 age- and sex-matched control patients (mean age +/- SEM: 38+/-2 years). The following variables were measured in both groups: QUS parameters at the heel (BUA; SOS; Stiffness Index, SI); bone mineral density (BMD) at both the lumbar spine (LS) and femoral neck (FN) by dual-energy X-ray absorptiometry; and serum markers of bone turnover (osteocalcin, procollagen type I N- and C-terminal propeptides (PINP and PICP), bone alkaline phosphatase (BAP), procollagen type I C-terminal telopeptide (ICTP) and urinary type I collagen C-telopepetide breakdown products (CTX)). Both BUA and SI were decreased in patients with Cushing's syndrome (p<0.01) but not SOS (p=0.08). BMD was also strongly decreased in Cushing's syndrome, at both the LS and FN (p<0.005). The two markers of bone turnover statistically significantly different between the two groups were osteocalcin (mean + SEM: 3.5 + 0.7 ng/ml (Cushing's syndrome) vs 6.4+/-0.5 ng/ml (controls, p<0.01)) and CTX (mean +/- SEM: 148.7+/-17.1 microg/mmol Cr (Cushing's syndrome) vs 220.8+/-22.9 microg/mmol Cr (controls), p<0.05). The areas under the receiver operating characteristic curve (AUC) were 0.72 (BUA), 0.73 (SI), 0.90 (BMD(LS)), 0.81 (BMD(FN)), 0.83 (osteocalcin) and 0.64 (CTX) respectively. AUC was significantly higher for BMD(LS) than for both BUA and SI (p<0.05). Conversely AUC was not statistically significantly different for BMDFN as compared with either BUA or SI. AUC was also higher for osteocalcin than for other markers of bone turnover. In conclusion, QUS of bone seems to be a relevant tool for assessing bone involvement in Cushing's syndrome. QUS does have a lower sensitivity compared with DXA, however, and the relevance of QUS cannot be ascertained until some longitudinal data are forthcoming. Except for CTX, the other new markers of bone turnover assessed in this study (PINP, PICP, BAP and ICTP) do not seem of interest in Cushing's syndrome.

Clinical application of biochemical markers of bone turnover

“…For example, markers of bone turnover may reflect changes in bone metabolism induced by oophorectomy (57,125), hyperparathyroidism (126,127), Paget's disease (128), physical exercise (129), immobilisation (32,130), alcoholism (131), smoking (132), vitamin D deficiency (33,35,37,133), chronic inflammatory bowel disease (134,135), chronic starvation (136), thyroid disorders (52,137) as well as the pharmacological effects of glucocorticosteroids (48,139,140), androgens (6,7,141), gonadotropin-releasing hormone agonists (142), warfarin (143), growth hormone or insulin-like growth factors (144). Bone turnover markers may be useful in the diagnosis and management of certain of the above conditions, but in most cases has not been rigorously examined.…”

Bone turnover in patients with endogenous Cushing’s syndrome before and after successful treatment

“…Bone formation, evaluated most frequently with osteocalcin (OC) measurements, was found to be greatly suppressed in most [3][4][5][6][7] but not all studies [8][9][10], while aminoterminal propeptide of type 1 procollagen was less suppressed or even normal in these patients. On the other hand, conflicting data have been reported on the rate of bone resorption in patients with endogenous hypercortisolism, as resorption markers have been found to be normal [5,6,11], decreased [6,7,12], and even increased [9,10,13,14]. These contradictory results may be explained by the use of various markers and laboratory techniques, the variable proportions of different subgroups of Cushing's syndrome (CS) and the differences in the severity of CS.…”

Quantitative Ultrasound of the Heel and Some Parameters of Bone Turnover in Patients with Acromegaly

“…QUS of the heel reflects trabecular bone status, bone quality and predicts fracture risk [7,8]. Numerous QUS studies have been carried out in postmenopausal osteoporosis and other endocrine disorders that affect bone metabolism, such as primary hyperparathyroidism and hyperthyroidism, or during pregnancy and lactation when hormonal status changes [9][10][11][12][13]15]. …”

“…QUS has been applied in some metabolic and hormonal bone diseases such as osteoporosis, Cushing's syndrome, hyperthyroidism and primary hyperparathyroidism [10][11][12][13]. To our knowledge QUS of the heel has not been studied in acromegaly.…”