Biochemical assessment of bone formation and resorption in acromegaly.

Ezzat, Shereen; Melmed, Shlomo; Endres, David B.; Eyre, David R.; Singer, Frederick R.

doi:10.1210/jcem.76.6.8501150

Cited by 81 publications

(76 citation statements)

References 39 publications

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“…Serum total calcium level is generally within the upper normal range and hypercalciuria is frequent in acromegalics [12][13][14]: this is due to the increased intestinal calcium absorption secondary to enhanced renal synthesis of 1,25 (OH) 2 vit D [4,8,15,16], although the increased bone resorption may contribute [3]. Furthermore, acromegalic patients show increased renal phosphate reabsorption [17] resulting in serum phosphate levels within or above normal range [18].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, acromegalic patients show increased renal phosphate reabsorption [17] resulting in serum phosphate levels within or above normal range [18]. Increased serum osteocalcin levels have been found in acromegalics [3,5,12,[19][20][21][22] as GH, IGF-I and 1,25 (OH) 2 vit D stimulate osteocalcin synthesis [23,24].…”

Section: Discussionmentioning

confidence: 99%

“…It is known that acromegalic patients show abnormalities in calcium-phosphate metabolism and morphologic skeleton alterations [3]. Pituitary adenectomy corrects many of these biochemical alterations [4,5].…”

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confidence: 99%

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Long-term Treatment of Acromegaly with Lanreotide: Evidence of Increased Serum Parathormone Concentration

et al. 2004

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Abstract. The somatostatin analogue lanreotide is effective in reducing growth hormone levels in patients with acromegaly. Acromegaly is characterized by calcium homeostasis alterations. The aim of our study was to evaluate the effects of lanreotide on bone turnover markers in a group of acromegalic patients and to verify a possible increase of intact parathormone (iPTH) levels in a transient or persistent way. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before treatment and on months 3 and 24. In short-term treatment (3 months), lanreotide significantly decreased GH, IGF-I, serum calcium, osteocalcin and alkaline phosphatase levels, but increased iPTH level (49 ± 16.7 vs pre-treatment 28.3 ± 7.6 ng/L, p<0.001). During long-term study (24 months) GH and IGF-I were significantly still low; serum calcium and alkaline phosphatase levels returned to pre-treatment levels. iPTH level was significantly still higher compared with pre-treatment (46.4 ± 9.2 vs 28.3 ± 7.6 ng/L, p<0.05). No changes were seen in serum albumin, creatinine and vitamin D during short and long term treatment. The changes of most bone markers during lanreotide treatment can be explained by the decrease of GH and IGF-I. The increase of iPTH concentration suggests that lanreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the lanreotide could contribute to this "secondary" hyperparathyroidism. The clinical relevance of these long-standing effects needs to be further investigated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long-term Treatment of Acromegaly with Lanreotide: Evidence of Increased Serum Parathormone Concentration

et al. 2004

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“…At the time of bone resorption, the carboxyterminal telopeptide of type I collagen (ICTP) is excreted through collagen degradation, and this excretion rate is considered a parameter of the rate of bone degradation [13]. The measurement of serum PICP and ICTP levels has been reported to be useful in evaluating bone metabolism in various diseases [14][15][16][17].…”

Section: Procollagen (Picp) Is Cleaved From Procollagen Moleculesmentioning

confidence: 99%

Relationship Between Serum Levels of Interleukin-6, Tumor Necrosis Factor-.ALPHA. and Bone Turnover Markers in Prostate Cancer Patients.

1998

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Abstract. To determine the relationship between the serum levels of Interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) and those of bone formation and resorption markers in prostate cancer patients, we measured the serum levels of the cytokines and examined their relationship to biochemical markers of bone turnover in 46 untreated patients with prostate cancer. The carboxy-terminal propeptide of type I procollagen (PICP) levels were used as a parameter of bone formation, and the carboxy-terminal telopeptide of type I collagen (ICTP) levels were used as a marker of bone resorption. The relationship of these markers to the degree of bone metastasis was also examined. The serum levels of IL-6, PICP, ICTP, and prostate-specific antigen (PSA) were significantly higher in the patients with prostate cancer with bone metastasis (n=23) than in the patients without bone metastasis (n=23). The serum levels of TNF-a in approximately 85% of the patients were under the detectable limit (5 pg/ml). The serum levels of IL-6 were not correlated with those of PICP or ICTP, but were related to the extent of bone metastasis. These results indicate that among patients with prostate cancer, IL-6 and TNF-a may not play major roles in the increased bone resorption in the patients with metastatic spread to bone. Our study thus demonstrated that the serum levels of IL-6 are closely related to the metastatic burden to osseous tissue in prostate cancer patients.

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“…Another original observation of our study was concerned with bone metabolism markers and their association with fractures. Previous studies demonstrated that active acromegaly was associated with increased calcium and phosphate serum levels, increased calciuria and markers of bone formation, and bone resorption (26,27,28,29,30,31). Bonadonna et al (14) found that fractured acromegalic women had higher serum bone alkaline phosphatase and urinary deoxypiridinoline and lower serum levels of vitamin D compared with non-fractured patients, but the study population was too small (36 women) to draw any real final conclusion.…”

Section: European Journal Of Endocrinologymentioning

confidence: 94%

GH receptor isoforms and skeletal fragility in acromegaly

Mormando¹,

Nasto²,

Bianchi³

et al. 2014

European Journal of Endocrinology

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Objective: Acromegaly is associated with an increased prevalence of vertebral fractures (VFs) in close relationship with GH hypersecretion. Two isoforms of the GH receptor (GHR) have been identified; the two isoforms differ or not by the expression of the protein fragment encoded by exon 3 of the GHR gene. Deletion of the exon 3 may influence the functional properties of the GHR and affect fracture risk in acromegalic patients. Design: A cross-sectional study was designed to investigate the association between the d3-GHR isoform and the prevalence of VFs in patients with acromegaly. Methods: In this study, 109 acromegalic patients were included (M/F, 48/61): 73 with controlled/cured acromegaly and 36 with active disease. GHR genotype was assessed in each patient. All patients were evaluated for VFs and bone mineral density at lumbar spine and hip. Serum IGF1 levels and bone metabolism markers were measured. A multivariate analysis was performed to establish risk factors for VFs in our population. Results: d3-GHR carriers showed an increased prevalence of VFs when compared with patients expressing full-length GHR (35/55 vs 12/54; P!0.001). The association between GHR deletion and VFs was demonstrated both in patients with active disease and in those with controlled/cured disease. Out of 35 patients who were prospectively evaluated, 13 (37.1%) developed incident VFs. The incidence of VFs was significantly higher in patients for whom the GHR gene has been deleted when compared with those harboring the fl gene (PZ0.04). In multivariate analysis, male sex (odds ratio (OR), 3.250; PZ0.041), IGF1 levels (OR, 1.183; PZ0.031), length of active diseases (OR, 1.038; PZ0.001), and d3-GHR genotype (OR, 3.060; PZ0.015) were all confirmed as risk factors of VFs in our population. Conclusions: This study suggests for the first time that exon 3 deletion of GHR may predispose patients with active and controlled acromegaly to a higher risk of VFs.

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Biochemical assessment of bone formation and resorption in acromegaly.

Cited by 81 publications

References 39 publications

Long-term Treatment of Acromegaly with Lanreotide: Evidence of Increased Serum Parathormone Concentration

Long-term Treatment of Acromegaly with Lanreotide: Evidence of Increased Serum Parathormone Concentration

Relationship Between Serum Levels of Interleukin-6, Tumor Necrosis Factor-.ALPHA. and Bone Turnover Markers in Prostate Cancer Patients.

GH receptor isoforms and skeletal fragility in acromegaly

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