Iliac crest bone mass and remodelling in acromegaly

Abstract

Iliac crest bone biopsies from 18 patients with active acromegaly, of whom 11 had received tetracycline double-labelling, were evaluated by quantitative histomorphometry and compared with age-and sex-matched normal controls. A significant increase (P<0.01) was found in both cortical (175%) and trabecular (130%) bone mass. In trabecular bone, resorption surfaces and active (tetracycline-labelled) and total formation surfaces were increased (P < 0.05 and P<0.01, respectively) causing an enhanced bone turn-over at tissue level (P < 0.01). The increased trabecular bone mass indicates a positive net balance per remodelling cycle and, therefore, larger than normal bone remodelling units, which in part may explain the increased bone turn-over at tissue level. The activity of the osteoblasts active in mineralization (the appositional rate) was increased (P<0.01) and positively related to the fasting serum growth hormone levels (Rs = 0.69, P < 0.05). The average activity of active and inactive osteoblasts (bone formation rate at basic metabolic unit (BMU) level) was insignificantly increased. The proportion of active (tetracycline labelled) to non\x=req-\ active formation surfaces was normal. The bone changes were unrelated to serum levels and urinary excretions of calcium and phosphorus or to renal excretion of total and non-dialyzable hydroxyproline or cAMP.The metabolic bone disease of acromegaly has over the years been the subject of repeated discussion. Radiological investigations have shown a coarsen¬ ing of trabecular patterns and increased radiolucency -especially of the vertebral bodies. This finding was interpreted by earlier investigators as evidence for osteoporosis (Scriver & Bryan 1935; Albright & Reifenstein 1948). A recent prestigious textbook also links acromegaly with osteoporosis (Avioli & Raisz 1980). Erdheim (1931) observed that in spite of radio¬ logical evidence of osteoporosis, the surface-near trabecular structures of the vertebral bodies were often thicker than normal. Consequently, he called the bone affection in acromegaly a 'sclerosing osteoporosis '. Remagen (1965) demonstrated that an increase in trabecular size could also be demon¬ strated in other parts of the skeleton.Recently the concept of osteoporosis in acro¬ megaly has been challenged. Doyle (1967) and Ikkos et al. (1974) using x-ray morphometry have demonstrated that the bone mass is actually in¬ creased in these patients. Using histomorphometry, Roelfsma et al. (1970) found increased values both for cortical and trabecular bone masses -results which were corroborated by Riggs et al. (1972) who studied a number of patients by bone densitometry and microradiography. Erdheim (1931) pointed to the increase in periosteal and enchondreal bone formation occur¬ ring in acromegaly. Riggs et al. (1972) and Delling & Schulz (1977) have presented evidence based on measurements of trabecular bone for an increase in bone turn-over. So far only one case report (Ramser et al. 1966) has described bone dynamics in acromegaly as evaluated after do...

Increased serum osteoprotegerin in disorders characterized by persistent immune activation or glucocorticoid excess--possible role in bone homeostasis

“…Although, in contrast to CS, acromegalic patients, at least in cortical bone, have a positive remodeling balance (27,28) and if raised OPG levels re¯ect a compensatory response to a negative remodeling balance, such a stimuli may be lacking in these patients. Also in GHD with a state of low bone turnover, OPG levels were within normal limits, suggesting that enhanced OPG activity may not play a pathogenic role in the inhibition of osteoclast activity in these patients.…”

Long-term maintenance of the anabolic effects of GH on the skeleton in successfully treated patients with acromegaly

“…In active acromegaly, histomorphometric studies report increased bone turnover at cortical, but not trabecular, sites (22,23). Cortical bone mass (24,25) and trabecular bone volume are increased (24) or normal, albeit with increased mean trabecular thickness (25). Recently, decreased trabecular biomechanical competence, apparent volumetric density and increased trabecular bone content of calcium were reported in active acromegaly, suggesting increased trabecular mineralisation (26).…”

“…Recently, decreased trabecular biomechanical competence, apparent volumetric density and increased trabecular bone content of calcium were reported in active acromegaly, suggesting increased trabecular mineralisation (26). However, the latter report contrasts with the normal or increased trabecular bone turnover in active acromegaly and the increased bone turnover observed in iliac crest biopsies during GH replacement in GHD patients (22,24,27). GH administration to aged rats leads to increased cortical bone mass and increased cortical bone strength, but cancellous bone is not significantly affected (28,29).…”

Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients

“…Details on gonadal status in patients and controls are given in Table 1. The duration of acromegaly (nZ55) was estimated to be (mean and range) 8 years (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The study was approved by the local ethical committee and conducted according to the Declaration of Helsinki II.…”