Biomedical subjects

J Bollerslev

Publications and source records attributed to J Bollerslev.

At least 19 recordsLinked to original sources

PubMed2006

No associations between OPG gene polymorphisms or serum levels and measures of osteoporosis in elderly Australian women.

Bone mass is the single most important risk factor for osteoporotic fractures in the elderly and is mainly influenced by genetic factors accounting for 40-75% of the inter-individual variation. Critical for the bone remodeling process is the balance between the newly discovered members of the tumor necrosis factor ligand and receptor superfamilies, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand, which mediate the effects of many upstream regulators of bone metabolism. In the present study, we evaluated the impact of sequence variations in the OPG gene on bone mass, bone-related biochemistry including serum OPG and fracture frequency in elderly Australian women. A total of 1101 women were genotyped for 3 different single nucleotide polymorphisms (SNP) within the OPG gene (G1181C, T950C and A163G). The effects of these SNPs and serum OPG on calcaneal quantitative ultrasound measurements, osteodensitometry of the hip and bone-related biochemistry were examined. We found no significant relationship between sequence variations in the OPG gene or serum OPG and bone mass, bone-related biochemistry or fracture frequency. Our findings confirm some recent publications investigating the same SNPs but diverge from others, indicating that generalization of the relationships found in this type of study must be done with caution and signify the importance of determining associations between polymorphisms and osteoporosis in different ethnic groups.

Absorptiometry, Photon↗

PubMed2006

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.

OBJECTIVE: Acromegaly is characterized by a persistent hypersecretion of GH and provides information on long-term effects of GH on bone metabolism. The aim of this study was to examine the effect of gonadal status and disease activity on bone metabolism in active acromegaly. METHODS: Seventy-three consecutive patients with active acromegaly: 40 women and 33 men (50 +/- 13 (mean +/- s.d.) and 49 +/- 10 years respectively) were evaluated and compared with age-, sex-, and body mass index (BMI)-matched controls by X-ray absorptiometry and biochemical analysis (markers of disease activity and bone turnover). RESULTS: We found that bone turnover, as evaluated by biochemical bone markers, is coupled and markedly increased in relation to disease activity in active acromegaly. Acromegalic women, but not men, were characterized by an increased bone area and slightly decreased bone mineral content resulting in significantly decreased bone mineral density (BMD) in the ultradistal radius, proximal radius, and total body. No differences in bone turnover or BMD were found between eu-and hypogonadal subjects. Multivariate analysis identified age, BMI, and gender as independent predictors of total BMD in acromegaly. CONCLUSION: Our study demonstrates a decreased total body BMD in women, not men, with active acromegaly, regardless of gonadal status or disease activity. Bone turnover is markedly increased in relation to disease activity, possibly counteracting the anabolic effects of excess GH/IGF-I in these subjects. We suggest more focus on biomechanical analyses when investigating endocrine disorders affecting bone size and distribution between compartments.

Acromegaly↗

PubMed2005

LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women.

Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exon 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357 A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-up period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures.

Absorptiometry, Photon↗

PubMed2005

Maternal anthropometric and metabolic factors in the first half of pregnancy and risk of neonatal macrosomia in term pregnancies. A prospective study.

OBJECTIVE: The prevalence of maternal overweight and fetal macrosomia is increasing. Fetal macrosomia is associated with increased risk of maternal and neonatal complications. The objective of the present study was to investigate if maternal metabolic parameters associated with maternal overweight were independent determinants of macrosomia (birth weight > 4500 g or above the 95 percentile of the z-score for standardized birth weight). DESIGN: Prospective population based cohort study of 2050 pregnancies and nested case control study. METHODS: Outcome measures were adjusted risks for macrosomia in relation to early second trimester maternal serum lipids, glucose and insulin (cohort study) and leptin and insulin-like growth factor (73 cases and 146 matched controls). RESULTS: Gestational diabetes was not independently associated with fetal macrosomia. First trimester body mass index (BMI), gestational weight gain and placental weight were associated with macrosomia. High serum insulin and non-high density lipoprotein (HDL)-cholesterol and low serum HDL-cholesterol were associated with increased risk of macrosomia independent of BMI, weight gain, placental weight and gestational diabetes. Slim women with macrosomic infants had higher insulin compared with those with normal weight infants. This relation was not found among obese women. Leptin was not associated with macrosomia after adjusting for maternal BMI. CONCLUSIONS: Blood parameters known to be associated with the metabolic syndrome were risk factors for macrosomia independent of maternal BMI.

Adult↗

PubMed2003

Calcium-sensing receptor gene polymorphism A986S does not predict serum calcium level, bone mineral density, calcaneal ultrasound indices, or fracture rate in a large cohort of elderly women.

Postmenopausal osteoporosis is a complex and heterogeneous disease influenced by multiple factors and related to peak bone mass achieved in early adult life, followed by a subsequent continuous bone loss. Genetic variance and polymorphisms have been shown to be of clinical significance for osteoporotic fragility fractures. Previous studies have related variations in the calcium sensor receptor (CASR) gene to circulating Ca levels and bone mass in young women and adolescent girls. The aim of this study was to investigate the impact of the A986S polymorphism of the CASR gene on calcium homeostasis and bone metabolism in elderly women. We studied the distribution of the A986S polymorphism in a large cohort of 1252 ambulatory Australian women in relation to biochemical markers of bone metabolism, bone mass evaluated by quantitative ultrasound measurements (QUS) and DXA of the hip, prevalent and 36-month incident fracture data. No effect of the polymorphism was found on circulating calcium level, renal Ca excretion, or biochemical markers of bone turnover. Moreover, A986S was not associated with bone mass or prevalent or incident fractures. Power calculations revealed that a difference in circulating calcium levels of 0.05 mmol/l, a difference in DXA bone density of 24 mg, and a 1.6-fold difference in fracture rate could have been detected with a power of 80%. In conclusion, in a large cohort of elderly women the A986S polymorphism of the CASR gene was not found to be significant for calcium homeostasis or bone mass. It is questioned whether the polymorphism has any clinical significance for postmenopausal osteoporosis.

Aged↗

PubMed2003

Growth hormone substitution increases gene expression of members of the IGF family in cortical bone from women with adult onset growth hormone deficiency--relationship with bone turn-over.

OBJECTIVE: To investigate the effects of growth hormone (GH) replacement therapy on bone matrix gene expression of insulin-like growth factors (IGFs) and markers of bone metabolism in women with adult-onset GH deficiency (GHD). DESIGN AND METHODS: Nineteen women, mean age 45 (range 24-56) years, were included in a double-blind, placebo-controlled parallel group study for 12 months. Biochemical markers were measured at baseline, 6 and 12 months. Bone biopsies were obtained and BMD was measured at baseline and after 12 months. RESULTS: Maximum responses were observed after 6 and 12 months, for bone resorptive and bone formative markers respectively. GH therapy enhanced gene expression in cortical bone of IGFs, GH-and calcitonin-receptor (CR) and osteoprotegerin (OPG), however with the most pronounced effects on CR and IGF-I. Changes in IGF-I gene expression during longitudinal follow-up were significantly correlated with changes in both circulating IGF-I (r = 0.82, p < 0.05), changes in markers of enhanced osteoclastic activity, measured both locally in bone (CR, r = 0.87, p < 0.01) and in serum (CTX-I, r = 0.86, p < 0.05), as well as serum bone ALP (r = 0.96, p < 0.01). CONCLUSIONS: This study indicates that both liver- and bone-derived IGF-I may be significant in mediating the effects of GH on bone metabolism in humans.

Adult↗

PubMed2003

Interleukin-1 receptor antagonist is associated with fat distribution in endogenous Cushing's syndrome: a longitudinal study.

The weight gain and visceral obesity associated with Cushing's syndrome (CS) has been linked to elevated plasma leptin levels, although the mechanism behind a central leptin resistance in these patients is unknown. Several studies describe interactions among the hypothalamic-pituitary-adrenal axis, leptin, and the IL-1 system. To investigate these interactions, we have evaluated changes in regional fat distribution, by DEXA, and the role of circulating cortisol, leptin, IL-1beta, and IL-1 receptor antagonist (IL-1Ra), in relation to these changes, in 27 (19 DEXA; 27 serum measurements) patients with CS, before and after surgical treatment (mean follow-up, 31 months; range, 5-80), and compared them with measurements of age-, sex-, and body mass index-matched healthy controls (also obtained longitudinally). We found that surgical treatment caused a decrease in all fat parameters, without changing lean body mass, and these changes were significantly larger than the so-called natural changes occurring in control subjects. These changes in CS patients were paralleled by decreases in cortisol, leptin, and IL-1Ra, whereas IL-1beta increased. Stepwise linear regression showed that serum IL-1Ra was strongly associated with regional fat distribution, and especially truncal fat mass, both at baseline and during treatment. In conclusion, the present study shows that treatment significantly changes body composition in CS patients by decreasing fat mass, especially in the truncal region, without major effects on lean body mass. We also show that circulating IL-1Ra is strongly associated with these changes, signifying a relationship among the hypothalamic-pituitary-adrenal axis, IL-1 system, and regional fat distribution in these patients.

Adipose Tissue↗

PubMed2003

Secondary osteoporosis in liver transplant recipients: a longitudinal study in patients with and without cholestatic liver disease.

BACKGROUND: Metabolic bone disease is one of the major long-term complications in liver transplant recipients, but it remains unclear which patients are at highest risk for developing severe bone disease following transplantation. METHODS: A total of 46 consecutive, adult patients with chronic liver disease accepted for a liver transplantation waiting list were prospectively included in the study. The patients were classified into two groups: group A--chronic cholestatic liver disease (n = 28), and group B--chronic non-cholestatic liver disease (n = 18). Bone mineral density (BMD) was measured at acceptance for the waiting list and at 3, 12 and 36 months following transplantation. Markers of bone turnover (serum-bone specific alkaline phosphatases (bALP), s-osteocalcin, s-1-collagen-C-terminal telopeptide (1-CTP) and urine N-terminal telopeptides u-Ntx) were measured at acceptance and at 3, 6, 12, 24 and 36 months following transplantation. BMD and markers of bone turnover were compared with similar values in a matched control group of 42 healthy individuals. RESULTS: BMD decreased significantly during the early post-transplantation period (median bone loss femoral neck (FN) 3 months post-transplant 8.5%). BMD levels declined slightly from 3 to 12 months following transplantation and increased thereafter. The relative bone loss was greatest among group B patients (relative bone loss FN 3 months post-transplant: group A, 8% versus group B, 13%; P = 0.04). At 36 months, 8/17 group A and 2/9 group B patients had BMD levels that exceeded the pretransplant levels (P = 0.12). The early bone loss was positively correlated with an increase in resorption markers (s-1-CTP and u-Ntx). Group B had higher levels of both s-1-CTP and u-Ntx at 3 and 6 months post-transplant than group A patients (P = 0.03). Bone formation markers increased slowly from 6 months post-transplant and onwards. Relative bone loss was positively correlated to total glucocorticoid dose during the first 3 months post-transplant. There were no differences in BMD between patients receiving tacrolimus versus those receiving cyclosporin A. CONCLUSION: Bone loss following liver transplantation is considerable in patients with both cholestatic and non-cholestatic liver disease, the first group has the poorest starting-point while the latter group has the greatest bone loss following transplantation. Bone loss is closely correlated with biochemical markers of bone resorption and total dose of glucocorticoids given post-transplant.

Adult↗

PubMed2002

Decreased trabecular bone biomechanical competence, apparent density, IGF-II and IGFBP-5 content in acromegaly.

BACKGROUND: Earlier studies on the effect of excess growth hormone (GH) on trabecular bone have been conflicting. Since insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in part mediate the effects of GH, the present study aimed to investigate trabecular bone composition of these growth factors in relation to biomechanical properties in acromegaly. MATERIALS AND METHODS: Trabecular bone biomechanical competence (compression test), apparent density (peripheral quantitative computed tomography, pQCT), and bone matrix contents of calcium (HCl hydrolysis) and IGFs (guanidinium-HCl extraction) were measured in iliac crest biopsies from 13 patients with active acromegaly (two women and 11 men, aged 21-61 years) and 21 age- and sex-matched controls (four women and 17 men, aged 23-64 years). RESULTS: Trabecular bone pQCT was reduced in acromegalic patients compared with controls (P = 0.005), as was biomechanical competence (P < 0.05 for all measures). These parameters were significantly positively correlated in both acromegalic patients and controls. The calcium content of trabecular bone was significantly increased in patients compared with controls. No significant differences were found in trabecular bone content of IGF-I, IGFBP-3, or osteocalcin. However, IGF-II and IGFBP-5 content was decreased (P < 0.001 and P < 0.05, respectively). CONCLUSIONS: The present study demonstrates reduced trabecular biomechanical competence and apparent density in acromegaly, supporting previous observations of an unfavourable effect of chronic excess GH on the axial skeleton. Furthermore, we demonstrate decreased trabecular bone content of IGF-II and IGFBP-5 in these patients. However, we found no direct causal relationship between trabecular bone density and bone content of IGF-system components.

Acromegaly↗

PubMed2002

Parathyroid adenoma in a subject with familial hypocalciuric hypercalcemia: coincidence or causality?

A middle-aged woman presented with a history of constipation, easy fatigue, depressive mood, lassitude, polydipsia, and polyuria. The patient posed a challenging diagnostic dilemma due to the presence of persistent severe hypercalcemia and relative lack of clinically manifested symptoms. Clinical, biochemical, and genetic examinations confirmed the diagnosis of familial hypocalciuric hypercalcemia as a result of C562Y calcium-sensing receptor mutation, and a coexisting parathyroid adenoma. After adenectomy, the patient's clinical situation improved markedly, and a modest equilibrium hypercalcemia persisted. This case presents an unusual combination of two relatively common endocrine disorders.

Adenoma↗

PubMed2002

Effects of 12 months of GH treatment on cortical and trabecular bone content of IGFs and OPG in adults with acquired GH deficiency: a double-blind, randomized, placebo-controlled study.

To investigate the effects of 12 months of GH treatment on cortical and trabecular bone content of IGFs, iliac crest bone biopsies were obtained from 25 patients with GH deficiency (9 women and 16 men; ages, 21-61 yr; mean, 46 yr) who were randomized to sc injections with GH (2 IU/m(2).d) or placebo for 12 months. Levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, osteocalcin, OPG, RANKL, and total protein were determined in extracts obtained after EDTA and guanidine hydrochloride extraction. Calcium was determined after HCl hydrolysis. Comparing changes during GH or placebo treatment, significant increases were observed during GH substitution for cortical and trabecular bone content of IGF-I [mean difference vs. placebo (mean +/- SEM), 97 +/- 30 and 72 +/- 38%] and OPG (mean difference vs. placebo, 109 +/- 59 and 51 +/- 19%). Also, a significant decline was found for cortical osteocalcin (mean difference vs. placebo, -49 +/- 22%) during GH treatment. In conclusion, our results indicate that long-term GH treatment increases the accumulation of IGF-I and OPG in cortical and trabecular bone in patients with GH deficiency, and this may in turn lead to an increase in bone mass and improved skeletal biomechanical competence.

Adult↗

PubMed2001

Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene.

Albers-Schönberg disease, or autosomal dominant osteopetrosis, type II (ADO II), is the most common form of osteopetrosis, a group of conditions characterized by an increased skeletal mass due to impaired bone and cartilage resorption. Following the assignment of the gene causing ADO II to chromosome 16p13.3, we now report seven different mutations in the gene encoding the ClCN7 chloride channel in all 12 ADO II families analysed. Additionally, a patient with the severe, autosomal recessive, infantile form of osteopetrosis (ARO) was identified as being homozygous for a ClCN7 mutation. From genotype-phenotype correlations, it seems that ADO II reflects a dominant negative effect, whereas loss-of-function mutations in ClCN7 do not cause abnormalities in heterozygous individuals. Because some ARO patients have mutations in both copies of the ClCN7 gene, ADO II is allelic with a subset of ARO cases.

Alleles↗

PubMed2001

Mapping of autosomal dominant osteopetrosis type II (Albers-Schönberg disease) to chromosome 16p13.3.

The osteopetroses are a heterogeneous group of conditions characterized by a bone-density increase due to impaired bone resorption. As well as the two or more autosomal recessive types, two autosomal dominant forms of osteopetrosis, differentiated by clinical and radiological signs, are described. Autosomal dominant osteopetrosis (ADO) type II, also known as "Albers-Schönberg disease," is characterized by sclerosis, predominantly involving the spine (vertebral end-plate thickening, or Rugger-Jersey spine), the pelvis ("bone-within-bone" structures), and the skull base. An increased fracture rate can be observed in these patients. By linkage analysis, the presence, on chromosome 1p21, of a gene causing ADO type II was previously suggested. However, analysis of further families with ADO type II indicated genetic heterogeneity within ADO type II, with the chromosome 1p21 locus being only a minor locus. We now perform a genomewide linkage scan of a French extended family with ADO type II, which allows us to localize an ADO type II gene on chromosome 16p13.3. Analysis of microsatellite markers in five further families with ADO type II could not exclude this chromosomal region. A summed maximum LOD score of 12.70 was generated with marker D16S3027, at a recombination fraction (straight theta) of 0. On the basis of the key recombinants in the families, a candidate region of 8.4 cM could be delineated, flanked by marker D16S521, on distal side, and marker D16S423, on the proximal side. Surprisingly, one of the families analyzed is the Danish family previously suggested to have linkage to chromosome 1p21. Linkage to chromosome 16p13.3 clearly cannot be excluded in this family, since a maximum LOD score of 4.21 at theta=0 is generated with marker D16S3027. Because at present no other family with ADO type II has proved to have linkage to chromosome 1p21, we consider the most likely localization of the disease-causing gene in this family to be to chromosome 16p13.3. This thus reopens the possibility that ADO type II is genetically homogeneous because of a single gene on chromosome 16p13.3.

Chromosome Mapping↗

PubMed2001

Increased levels of biochemical markers of bone turnover in relation to persistent immune activation in common variable immunodeficiency.

BACKGROUND: Based on the involvement of cytokines and growth factors in bone homeostasis, we hypothesised that patients with common variable immunodeficiency (CVI), characterised by persistent immune activation in vivo, may have disturbed bone metabolism as evaluated by biochemical markers of bone turnover. MATERIALS AND METHODS: Serum levels of tumour necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), bone-specific alkaline phosphatase (B-ALP), osteocalcin, carboxyterminal crosslinking telopeptide of type I collagen (CTX-I), insulin-like growth factor (IGF)-I and IGF binding protein-3 (IGFBP-3) were measured in 25 patients with CVI and compared to 25 age- and sex-matched healthy controls. RESULTS: Patients with CVI had significantly higher serum levels of CTX-I and B-ALP, and significantly lower serum levels of IGF-I and IGFBP-3 compared to controls as shown in cross-sectional, and as for B-ALP and CTX-I, also during longitudinal testing. No differences were observed for osteocalcin between the two groups. The elevated B-ALP and decreased IGF-I and IGFBP-3 levels were most pronounced in a subgroup of CVI patients characterised by persistent activation of proinflammatory cytokines in vivo. Raised B-ALP and decreased IGF-I and IGFBP-3 were also significantly correlated with enhanced IL-6 and TNF-alpha levels in these patients. CONCLUSIONS: The present study suggests that persistent immune activation in vivo, with raised levels of proinflammatory cytokines, may be related to disturbed bone homeostasis in CVI patients, further supporting an interaction between immune related mediators and bone metabolism in humans.

Adult↗

PubMed2001

Leptin response to endogenous acute stress is independent of pituitary function.

There are close interactions between the adipocyte-derived hormone, leptin, and the anterior pituitary, especially the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the relationship between the sympathetic adrenergic system and serum leptin levels, dependent on the function of anterior pituitary hormone axes, in 27 patients without a history of a hormone-secreting pituitary adenoma or other underlying endocrine disease. Based on responses in a routine insulin hypoglycemia test (ITT), the patients were classified as hypopituitary (HP; n=15), growth hormone deficient (GHD; n=6) or controls (CTR; 6 patients with normal responses). Nadir plasma glucose was 1.5+/-0.1 mmol/l at the time of maximum hypoglycemia. Each group had a significant increase in plasma epinephrine; however the magnitude of change was significantly higher in GHD (6.066+/-1.633 nmol/l) compared with HP patients (1.781+/-0.492 nmol/l) (P<0.01). The rise in norepinephrine was delayed (60 min) in the HP and CTR groups. However, in GHD patients there was a considerable increase at the time of hypoglycemia which was significantly different from HP (P<0.001) and CTR (P<0.05) patients. The increase in catecholamines was followed by a quick and significant decrease in serum leptin levels 45 min after an i.v. bolus injection of insulin in HP patients (-4.7+/-2.5%, P<0.05), which was significantly sustained after 60 min (-5.6+/-2.5%, P<0.05). In CTR patients there was a significant decrease in serum leptin levels 60 min after i.v. insulin (-14.4+/-6.9%, P<0.05), while no significant response was observed in the GHD group, although 5 of 6 patients had decreased levels at 45 and 60 min. No differences between the groups were found by ANOVA. In conclusion, an acute increase in endogenous circulating catecholamines is associated with a quick decrease in serum leptin levels. Intact anterior pituitary function seems not to be essential for this hitherto poorly understood mechanism.

Adrenocorticotropic Hormone↗

PubMed2001

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

OBJECTIVE: To investigate the possible role of osteoprotegerin (OPG) in bone metabolism in humans by measuring serum levels of OPG in five well-characterized patient populations with known or suspected pathology in bone homeostasis, but with differences in the pathogenesis of these disturbances. DESIGN: The study comprised 34 patients with Cushing's syndrome (CS), 24 acromegalic patients, 16 patients with growth hormone deficiency (GHD), 29 HIV-infected patients, 25 patients with common variable immunodeficiency (CVI) and 59 age- and sex-matched healthy controls (CTR). METHODS: Serum levels of tumor necrosis factor (TNF)-alpha, OPG, C-terminal telopeptides of Type-I collagen (CTX-I) and osteocalcin were determined in all study subjects as well as cortisol (CS and CTR) and IGF-I (acromegaly, GHD and CTR). RESULTS: OPG levels were significantly elevated in both CVI (median increase approximately 32%, P < 0.05) and HIV-infected patients with especially high levels in the latter group ( approximately 52%, P < 0.001), significantly correlated with increased TNFalpha levels (r = 0.47, P < 0.02). Also CS patients had elevated serum OPG ( approximately 24%, P < 0.01), significantly correlated with increased serum cortisol (r = 0.35, P < 0.05). In contrast, OPG levels in acromegalic and GHD patients were not different from healthy controls. No relationships were found between OPG levels and CTX-I or osteocalcin. CONCLUSIONS: These findings suggest that enhanced OPG levels may be a compensatory response to enhanced osteoclast activity or negative bone remodeling balance in some conditions, but may also be a parameter of enhanced activity in the OPG system possibly correlated to enhanced activity of other members of the TNF family.

Acromegaly↗

PubMed2000

[Marginal primary hyperparathyroidism. Indication for treatment?].

Non familial primary hyperparathyroidism (pHPT) is often diagnosed accidentally by serum calcium screening. Som patients have marginally elevated calcium values, normal renal function, no renal stone disease and no clinical signs of bone disease. Bone densitometry reveals slightly reduced bone mineral content. Long time observation may show no progression. Observation is recommended due to the potentially stationary and symptomfree condition. Recent investigations have however shown that pHPT is associated with cardiac changes and elevated risk of cardiovascular death. Neuropsychiatric changes influencing level of function and quality of life have been demonstrated. There is therefore a substantial need for re-evaluation of the natural course of apparent asymptomatic pHPT and the effect of parathyroid surgery.

Bone Density↗

PubMed2000

[Acromegaly--diagnosis and treatment].

BACKGROUND: Acromegaly is a rare but clinically important disease caused by growth hormone hypersecretion, usually from a pituitary adenoma. The condition is associated with increased morbidity and mortality. MATERIAL AND METHODS: The prevalence of acromegaly is estimated to be 4-6 cases per million per year. The diagnosis is based on glucose-suppressed plasma growth hormone. When the diagnosis is confirmed, MR imaging of the pituitary gland is performed. RESULTS: Standard treatment is transsphenoidal microsurgery; however, radicality is often difficult because of extensive tumour growth. Preoperative administration of somatostatin analogues may improve the surgical outcome. INTERPRETATION: We have initiated a randomized, prospective study to elucidate this adjuvant treatment. Somatostatin analouges are required in the case of postoperative activity. This treatment is without tachyphylaxis and has few side effects. Alternatively, dopamine agonists such as bromocriptine can be used, especially in mixed tumours coproducing prolactin. Newer, more specific dopamine agonists are currently being evaluated. Radiation therapy may be required in large, unresectable tumours, but the effects are slow-acting, and almost all patients develop hypopituitarism. Gamma knife radiosurgery seems promising for stopping tumour growth as well as for decreasing excessive hormone production. However long-time follow-up results are so far lacking.

Acromegaly↗