Long-term excess of endogenous calcitonin in patients with medullary thyroid carcinoma does not affect bone mineral density

Abstract

In a cross-sectional study of 39 patients with medullary thyroid carcinoma (MTC), we have investigated the effects of long-term calcitonin excess on bone mineral density. Bone mineral density was measured by dual X-ray absorptiometry at the lumbar spine between the second and fourth vertebra and by single photon absorptiometry at the distal forearm. The mean observation time of each patient between diagnosis of tumour and measurement of bone mineral density was 62.4 months (range 1-158 months). The mean calcitonin serum level was 14.4 micrograms/l at the time of measurement of bone mineral density. All patients were substituted with 150-200 micrograms L-thyroxine daily. At both sites, the mean bone mineral densities of all patients with MTC were not significantly different from controls. Patients with normal calcitonin levels (below 0.2 micrograms/l) after treatment had a normal bone mineral density of the spine but significantly (P less than 0.05) reduced bone mineral density values of the forearm. This was due to the decreased body surface areas of patients in this subgroup. Patients with multiple endocrine neoplasia type IIa had significantly higher bone mineral densities. Other bone-influencing factors, such as postoperative hypoparathyroidism, calcium intake, diarrhoea, menopause, tumour stage, previous anti-tumour treatment, or thyroxine substitution dose, did not affect bone mineral density. We thus conclude that long-term excess of endogenous calcitonin in patients with MTC has no positive effect on bone mineral density.

Gastric Acid, Calcium Absorption, and Their Impact on Bone Health

“…This is corroborated by fundamental observations during conditions of decreased or increased calcitonin levels, neither of which result in an appreciable phenotype in terms of calcium balance. For example, patients with medullary carcinomas of the thyroid (MTC), a tumor of the thyroid C-cells resulting in the hypersecretion of calcitonin, were shown to have normal bone mineral densities (1176). Animal studies further substantiate this conundrum.…”

Sphingosine 1-phosphate signaling in bone remodeling: multifaceted roles and therapeutic potential

“…The hormone calcitonin is a known calcium-lowering factor, exerting its effect via the calcitonin receptor, and acting as an inhibitor of bone resorption [91]. However, in contradiction with the clearly defined pharmacologic mode of action, in patients with long-term excess of calcitonin due to medullary thyroid cancer bone mineral density is normal [92]. In line with physiological observations, the cell type-specific deletion of calcitonin receptor in mouse osteoclasts resulted in an increase in trabecular bone volume; furthermore, S1P release by osteoclasts was enhanced [89].…”

The Effect of Levothyroxine Therapy on Bone Mineral Density: A Systematic Review of the Literature

“…In most cross-sectional studies suppressive treatment had no effect on trabecular bone at central (Abugassa et al, 1993;De Rosa et al, 1995;Florkowski et al, 1993;Franklyn et al, 1992;Frusciante et al, 1998;Gam et al, 1991;Giannini et al, 1994;Görres et al, 1996;Hawkins et al, 1994;Langdahl et al, 1996;Lecomte et al, 1995;Lehmke et al, 1992;Marcocci et al, 1994;1997;Nuzzo et al, 1998;Schneider et al, 1995;Toivonen et al, 1998;Wüster et al, 1992) and peripheral sites (Radetti et al, 1993;Schneider et al, 1995;Wüster et al, 1992). The only study examining the calcaneus reported partial negative effects (Lehmke et al, 1992).…”

“…Results from cross-sectional studies on the effects of replacement therapy on trabecular bone were controversial, with no ef-fects at the lumbar spine (Franklyn et al, 1992;Gam et al, 1991;Hanna et al, 1998;Hawkins et al, 1994;Kung and Pun, 1991;Langdahl et al, 1996;Ribot et al, 1990;Schneider et al, 1995;Wüster et al, 1992) and ultradistal radius (Radetti et al, 1993;Schneider et al, 1995;Wüster et al, 1992), and reduced bone mineral density mainly in older and/or poor quality studies (Campos-Pastor et al, 1993; Demeester-Mirkine et al, 1990; Franklyn et al, 1994;Greenspan et al, 1991;Mirzaei et al, 1999;Schneider et al, 1994). The only study using QUS found lower ªbone mineral densityº at the calcaneus (Hadji et al, 2000).…”

“…Controversial effects of replacement therapy were also reported in cross-sectional studies at central, mixed cortical/trabecular sites suggesting no influence (Franklyn et al, 1992 , 1994). By contrast, the distal radius mostly remained unaffected (Grant et al, 1993;Langdahl et al, 1996;Wüster et al, 1992). Longitudinal studies also showed conflicting results at different sites of the hip, no effects (Bauer et al, 1997;Fowler et al, 1996;Guo et al, 1997;Rosen et al, 1998;Tümer et al, 1999), and also partial or overall negative effects (Duncan et al, 1994;Garton et al, 1994;Jodar et al, 1998;Ribot et al, 1990), and again no effects at the distal radius (Fujiyama et al, 1995a;1995b;Jodar et al, 1998;Saggese et al, 1996;Toh and Brown, 1990).…”