The Effect of Aromatase Inhibition on Sex Steroids, Gonadotropins, and Markers of Bone Turnover in Older Men1

2001 ◽  
Vol 86 (6) ◽  
pp. 2869-2874
Author(s):  
Pamela Taxel ◽  
Dayna G. Kennedy ◽  
Pamela M. Fall ◽  
Alice K. Willard ◽  
Jonathan M. Clive ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Turnover ◽  
Older Men ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Type I ◽  
Aromatase Inhibition ◽  
Bone Specific Alkaline Phosphatase ◽  
Type I Procollagen

There is evidence that estrogen decreases bone turnover in men as well as women. We therefore hypothesized that older men would show increased bone resorption in response to inhibition of the aromatase enzyme, which converts androgens to estrogen. Fifteen eugonadal men over 65 yr were treated for 9 weeks with 2.0 mg/day of anastrozole, an aromatase inhibitor. After 9 weeks of treatment, there were significant decreases in estradiol, estrone, and sex hormone-binding globulin levels by 29%, 73%, and 16%, respectively, and total testosterone increased significantly by 56%. Despite the limited decrease of estrogen and the increase in testosterone, C-telopeptide of type 1 collagen showed a progressive significant increase of 11%, 24%, and 33% (P for trend = 0.033) above baseline at 3, 6, and 9 weeks, respectively. N-telopeptide of type 1 collagen values were highly correlated with C-telopeptide of type 1 collagen, but the change in N-telopeptide of type 1 collagen was not statistically significant. Bone-specific alkaline phosphatase and N-terminal type I procollagen peptides showed significant decreases of 8% and 11% of baseline at 9 weeks. Osteocalcin decreased significantly by 30% at 18 weeks. We conclude that aromatase inhibition can reduce estrogen levels in older men, but this effect is limited, perhaps because of feedback stimulation of testosterone production, and that endogenous estrogen derived from aromatization of testosterone plays a role in bone metabolism of older men by limiting the rate of bone resorption.

scholarly journals SAT-021 Effects of E2/P4 Oral Capsules on Bone Turnover in Women with Vasomotor Symptoms

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ginger Constantine ◽  
Michael R McClung ◽  
Risa Kagan ◽  
Shelli Graham ◽  
Brian Bernick ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Osteoporotic Fractures ◽  
Vasomotor Symptoms ◽  
Type I ◽  
Bone Specific Alkaline Phosphatase ◽  
Type I Procollagen ◽  
Turnover Markers ◽  
Mean Differences ◽  
Post Hoc

Abstract Menopausal hormone therapy slows bone turnover and reduces the risk of osteoporotic fractures. The objective of this post hoc analysis was to evaluate bone turnover markers (BTM) in the phase 3 REPLENISH trial, which evaluated vasomotor symptoms (VMS) with an oral estradiol/progesterone (E2/P4) in postmenopausal women with a uterus. Eligible women for this analysis had ≥50 moderate to severe VMS/week, <5 years since last menstrual period, and BTM measurements at baseline, and months 6 and 12. Percent changes for 3 BTM (bone specific alkaline phosphatase [BSAP], C-terminal telopeptide of type I collagen [CTX-1], and N-terminal propeptide of type I procollagen [PINP]) assessed by immunoassay methods were evaluated from baseline to months 6 and 12 for the 1/100, 0.5/100 and placebo groups. A total of 157 women (40–61 years, 69% White) were analyzed (56 for each 1/100 and 0.5/100; 45 for placebo). Mean baseline values ranged from 14.0–14.3 U/L for BSAP, 0.34–0.39 ng/mL for CTX-1, and 76.9–79.3 ng/mL for PINP. Mean differences in percent change from baseline versus placebo significantly decreased with both E2/P4 doses for all 3 BTM at months 6 and 12. Mean differences from placebo for E2/P4 at months 6/12 ranged from -8.1% to -17.8% for BSAP (all, P≤0.02), -30% to -41% for CTX-1 (all, P≤0.001), and -14% to -29% for PINP (all, P≤0.007). REPLENISH data provide support for a potential skeletal benefit of E2/P4 when used for the treatment of moderate to severe VMS.

scholarly journals Early and Sustained Changes in Bone Metabolism After Severe Burn Injury

2016 ◽  
Vol 101 (4) ◽  
pp. 1506-1515 ◽  
Author(s):  
Gabriela Katharina Muschitz ◽  
Elisabeth Schwabegger ◽  
Roland Kocijan ◽  
Andreas Baierl ◽  
Hervé Moussalli ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Burn Injury ◽  
Fibroblast Growth Factor 23 ◽  
Type I ◽  
Severe Burn ◽  
Bone Specific Alkaline Phosphatase ◽  
Type I Procollagen ◽  
Male Patients ◽  
Severe Burn Injury

Abstract Context: Severe burn injury causes a massive stress response, consecutively heightened serum levels of acute phase proteins, cortisol, and catecholamines with accompanying disturbance in calcium metabolism. Objective: Evaluation of early and prolonged changes of serum bone turnover markers (BTMs) and regulators of bone metabolism. Design: Longitudinal observational design. Setting: University clinic. Patients: A total of 32 male patients with a median age of 40.5 years and a median burned total body surface area of 40% (83% patients with full thickness burn injury). Interventions: None. Main Outcome Measures: Comparison of changes of BTM/regulators of bone metabolism in the early (d 2–7) and prolonged (d 7–56) phases after trauma. Results: All investigated BTM/regulators significantly changed. During the early phase, pronounced increases were observed for serum type 1 collagen cross-linked C-telopeptide, intact N-terminal propeptide of type I procollagen, sclerostin, Dickkopf-1, bone-specific alkaline phosphatase, fibroblast growth factor 23, and intact parathyroid hormone levels, whereas 25-hydroxyvitamin D, albumin, serum, and ionized calcium levels decreased. Changes of osteoprotegerin, osteocalcin, and phosphate were less pronounced but remained significant. In the prolonged phase, changes of intact N-terminal propeptide of type I procollagen were most pronounced, followed by elevated sclerostin, osteocalcin, bone-specific alkaline phosphatase, and lesser changes for albumin levels. Calcium and ionized calcium levels tardily increased and remained within the limit of normal. In contrast, levels of intact parathyroid hormone, fibroblast growth factor 23, C-reactive protein, and to a lesser extent serum type 1 collagen cross-linked C-telopeptide and phosphate levels declined significantly during this phase of investigation. Conclusions: Ongoing changes of BTM and regulators of bone metabolism suggest alterations in bone metabolism with a likely adverse influence on bone quality and structure in male patients with severe burn injuries.

scholarly journals Serum Sclerostin and Bone Turnover in Latent Autoimmune Diabetes in Adults

2018 ◽  
Vol 103 (5) ◽  
pp. 1921-1928 ◽  
Author(s):  
Nicola Napoli ◽  
Rocky Strollo ◽  
Giuseppe Defeudis ◽  
Gaetano Leto ◽  
Chiara Moretti ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I Collagen ◽  
Autoimmune Diabetes ◽  
Positive Trend ◽  
Type I ◽  
Cross Sectional ◽  
Latent Autoimmune Diabetes

Abstract Purpose Bone formation is impaired in both type 1 diabetes and type 2 diabetes (T2D), whereas sclerostin, an antagonist of bone formation, is increased in T2D only. No data are available on latent autoimmune diabetes in adults (LADA), an autoimmune type of diabetes that may clinically resemble T2D at diagnosis. We evaluated serum sclerostin and bone turnover markers in LADA compared with those in T2D and whether metabolic syndrome (MetS) affects sclerostin in T2D or LADA. Methods This cross-sectional study included 98 patients with T2D and 89 with LADA from the Action LADA and Non Insulin Requiring Autoimmune Diabetes cohorts. Patients were further divided according to MetS status. Nondiabetic participants (n = 53) were used as controls. Serum sclerostin, bone formation (pro-collagen type 1 N-terminal propeptide [P1NP]), and bone resorption (C-terminal telopeptide of type I collagen [CTX]) were analyzed. Results Patients with T2D had higher sclerostin than did those with LADA [P = 0.0008, adjusted for sex and body mass index (BMI)], even when analysis was restricted to patients with MetS (adjusted P = 0.03). Analysis of T2D and LADA groups separately showed that sclerostin was similar between those with and those without MetS. However, a positive trend between sclerostin and number of MetS features was seen with T2D (P for trend = 0.001) but not with LADA. Patients with T2D or LADA had lower CTX than did controls (P = 0.0003) and did not have significantly reduced P1NP. Sclerostin was unrelated to age or hemoglobin A1c but was correlated with BMI (ρ = 0.29; P = 0.0001), high-density lipoprotein (ρ = −0.23; P = 0.003), triglycerides (ρ = 0.19; P = 0.002), and time since diagnosis (ρ = 0.32; P < 0.0001). Conclusions Patients with LADA presented lower bone resorption than did controls, similar to patients with T2D. Sclerostin is increased in T2D but not in LADA, suggesting possible roles on bone metabolism in T2D only.

scholarly journals Recombinant Human Chorionic Gonadotropin But Not Dihydrotestosterone Alone Stimulates Osteoblastic Collagen Synthesis in Older Men with Partial Age-Related Androgen Deficiency

2004 ◽  
Vol 89 (6) ◽  
pp. 3033-3041 ◽  
Author(s):  
Christian Meier ◽  
Peter Y. Liu ◽  
Lam P. Ly ◽  
James de Winter-Modzelewski ◽  
Mark Jimenez ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Turnover ◽  
Type I Collagen ◽  
Older Men ◽  
Type I ◽  
Androgen Deficiency ◽  
Age Related ◽  
Aging Men ◽  
To Receive ◽  
Androgen Supplementation

Abstract Several randomized trials of androgen supplementation in older men have been undertaken. However, the relative contributions of testosterone (T) and estrogens on bone metabolism in aging men are controversial. Within the setting of two double-blind, placebo-controlled studies, we evaluated the effect of dihydrotestosterone (DHT) and recombinant human chorionic gonadotropin (rhCG) on bone turnover in healthy, community-dwelling older men with partial androgen deficiency (total T ≤ 15 nmol/liter). In the first study, 35 men (age 68.3 ± 6.8 yr; baseline T, 13.9 ± 3.3 nmol/liter) were randomized to receive either daily transdermal DHT (n = 17) or placebo for 3 months. In the second study, 40 men (age 67.4 ± 5.4 yr; baseline T, 11.4 ± 2.2 nmol/liter) were randomized to receive either rhCG sc (n = 20), two injections weekly, or placebo for 3 months. The following parameters were measured before, monthly during, and 1 month after treatment: serum T, estradiol (E2), and LH; markers of bone formation, serum amino-terminal propeptide of type I procollagen (S-PINP) and osteocalcin; markers of bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline. Compared with placebo, treatment with DHT significantly increased serum DHT and suppressed LH and T levels, whereas E2 concentrations and markers of bone turnover did not change. In contrast, rhCG therapy significantly increased both T and E2, with the increases in E2 being supraphysiological. At the same time, rhCG significantly increased S-PINP concentrations with peak levels after 1 month (Δ40%; P = 0.02 compared with placebo). In contrast, serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change. The change in S-PINP levels correlated with the change in E2 levels (r = 0.59; P = 0.02) but not with a change in T. We conclude that in older men with partial age-related androgen deficiency, rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption. In contrast, treatment with a pure, nonaromatizable androgen (DHT) has no effect on bone turnover despite a 20-fold increase in serum levels. Bone resorption was not accelerated during unchanged (DHT) or increased (rhCG) E2 levels, suggesting that minimal E2 levels are needed to maintain stable resorption, although direct androgen receptor-mediated effects cannot be excluded. If androgen supplementation is required for aging men, aromatizable androgens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone.

scholarly journals Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calcium-regulating hormones and bone turnover markers

2002 ◽  
Vol 174 (2) ◽  
pp. 353-359 ◽  
Author(s):  
H Uemura ◽  
T Yasui ◽  
M Kiyokawa ◽  
A Kuwahara ◽  
H Ikawa ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Turnover ◽  
Gestational Age ◽  
Type I Collagen ◽  
Inhibitory Factor ◽  
Type I ◽  
Normal Range ◽  
Maternal Circulation ◽  
Bone Specific Alkaline Phosphatase ◽  
Pregnancy And Lactation

Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/ OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during pregnancy (at 8-11 weeks, at 22-30 weeks, at 35-36 weeks and immediately before delivery) and lactation (at 4 days and at 1 month postpartum). Serum intact parathyroid hormone levels did not change and were almost within the normal range in this period. In contrast, serum 1,25-dihydroxyvitamin D levels increased with gestational age and were above the normal range during pregnancy. After delivery, they fell rapidly and significantly (P<0.01) to the normal range. The levels of serum bone-specific alkaline phosphatase, one of the markers of bone formation, increased with gestational age. After delivery, these levels were further increased at 1 month postpartum. The levels at 1 month postpartum were significantly higher than those at 8-11 and 22-30 weeks of pregnancy (P<0.01 and P<0.05 respectively). The levels of serum C-terminal telopeptides of type I collagen, one of the markers of bone resorption, did not change during pregnancy. After delivery, they rapidly and significantly (P<0.01) rose at 4 days postpartum, and had then fallen by 1 month postpartum. Circulating OPG/OCIF levels gradually increased with gestational age and significantly (P<0.01) increased immediately before delivery to 1.40+/-0.53 ng/ml (means+/-S.D.) compared with those in the non-pregnant, non-lactating controls (0.58+/-0.11 ng/ml). After delivery, they fell rapidly to 0.87+/-0.27 ng/ml at 4 days postpartum and had fallen further by 1 month postpartum. These results suggest that the fall in OPG/OCIF levels may be partially connected with the marked acceleration of bone resorption after delivery.

scholarly journals In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study

2007 ◽  
Vol 156 (5) ◽  
pp. 585-594 ◽  
Author(s):  
Bu B Yeap ◽  
Osvaldo P Almeida ◽  
Zoë Hyde ◽  
Paul E Norman ◽  
S A Paul Chubb ◽  
...  
Keyword(s):  
Free Testosterone ◽  
Older Men ◽  
Early Morning ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Limited Data ◽  
Cross Sectional ◽  
Testosterone Concentration ◽  
Age Related ◽  
Clinical Consequences

Objective: An age-related decline in serum total and free testosterone concentration may contribute to ill health in men, but limited data are available for men > 70 years of age. We sought to determine the distribution and associations of reduced testosterone concentrations in older men. Design: The Health in Men Study is a community-representative prospective cohort investigation of 4263 men aged ≥ 70 years. Cross-sectional hormone data from 3645 men were analysed. Methods: Early morning sera were assayed for total testosterone, sex hormone binding globulin (SHBG) and LH. Free testosterone was calculated using the Vermeulen method. Results: Mean (± s.d.) serum total testosterone was 15.4 ± 5.6 nmol/l (444 ± 162 ng/dl), SHBG 42.4 ± 16.7 nmol/l and free testosterone 278 ± 96 pmol/l (8.01 ± 2.78 ng/dl). Total testosterone correlated with SHBG (Spearman’s r = 0.6, P < 0.0001). LH and SHBG increased with age (r = 0.2, P < 0.0001 for both). Instead of declining, total testosterone increased marginally (r = 0.04, P = 0.007) whilst free testosterone declined with age (r = −0.1, P < 0.0001). Free testosterone was inversely correlated with LH (r = −0.1, P < 0.0001). In multivariate analyses, increasing age, body mass index (BMI) and LH were associated with lower free testosterone. Conclusions: In men aged 70–89 years, modulation of androgen action may occur via an age-related increase in SHBG and reduction in free testosterone without a decline in total testosterone concentration. Increasing age, BMI and LH are independently associated with lower free testosterone. Further investigation would be required to assess the clinical consequences of low serum free testosterone, particularly in older men in whom total testosterone may be preserved.

scholarly journals Serum 25(OH)D3 vitamin status of elderly Finnish women is suboptimal even after summer sunshine but is not associated with bone density or turnover

2010 ◽  
Vol 162 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Tuula Pekkarinen ◽  
Ursula Turpeinen ◽  
Esa Hämäläinen ◽  
Eliisa Löyttyniemi ◽  
Henrik Alfthan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Density ◽  
Bone Turnover ◽  
Population Based ◽  
Type I ◽  
Vitamin D Status ◽  
Mineral Density ◽  
Type I Procollagen ◽  
Before And After ◽  
Before And After Summer

ObjectiveConcentrations of 50 and 75 nmol/l are proposed as serum 25-hydroxyvitamin D (25(OH)D) target for older people from the view of bone health. We evaluated vitamin D status of elderly Finnish women in light of these definitions, its relationship to bone mineral density (BMD) and turnover, and improvement by summer sunshine.DesignPopulation-based study.MethodsA total of 1604 ambulatory women aged 62–79 years were studied; 66% used vitamin D supplements. Serum 25(OH)D3was measured with HPLC before and after summer, and heel BMD in spring. In subgroups, serum parathyroid hormone (PTH) and type I procollagen aminoterminal propeptide (PINP) were analyzed.ResultsIn spring, 60.3% of the women had 25(OH)D3≤50 nmol/l, and the target of 75 nmol/l was reached by 9.1%. For supplement users, the respective numbers were 52.1 and 11.9%. Serum 25(OH)D3did not determine BMD or bone turnover measured by serum PINP. Summer sunshine increased serum 25(OH)D3by 17.4% (P<0.0001), but in autumn 84% of the subjects remained under the target of 75 nmol/l. In supplement users, PTH remained stable but decreased in others during summer (P=0.025).ConclusionsVitamin D status of elderly Finnish women is suboptimal if 25(OH)D3levels of 50 or 75 nmol/l are used as a threshold. It is moderately increased by supplement intake and summer sunshine. However, 25(OH)D3concentrations did not influence bone density in terms of serum PINP and bone turnover rate.

Biochemical markers of bone turnover following high-dose chemotherapy and autografting in multiple myeloma

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2697-2702 ◽  
Author(s):  
Richard E. Clark ◽  
Angela J. Flory ◽  
Edwina M. Ion ◽  
Barry E. Woodcock ◽  
Brian H. Durham ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Turnover ◽  
High Dose Chemotherapy ◽  
Marrow Transplant ◽  
High Dose ◽  
Creatinine Concentration ◽  
Bone Specific Alkaline Phosphatase ◽  
Osteoblast Activity ◽  
Markers Of Bone Turnover ◽  
High Dose Melphalan

Abstract The effect of high-dose chemotherapy and autografting on bone turnover in myeloma is not known. A study of 32 myeloma patients undergoing blood or marrow transplant (BMT), conditioned with high-dose melphalan, was done. Bone resorption was assessed by urinary free pyridinoline (fPyr) and deoxypyridinoline (fDPyr), expressed as a ratio of the urinary creatinine concentration. Bone formation was assessed by serum concentration of procollagen 1 extension peptide (P1CP) and bone-specific alkaline phosphatase (BSAP). Eighteen cases had normal fPyr and fDPyr at transplant, and in all but one of these cases the level remained normal throughout subsequent follow-up. In contrast, in 14 cases urinary fPyr and fDPyr levels were increased at transplant. In these cases, both fPyr and fDPyr fell to normal levels over the next few months (P = .0009 and .0019, respectively). fPyr and fDPyr levels at transplant and their trends post-BMT were unrelated to the use of pre-BMT or post-BMT bisphosphonate or post-BMT interferon. Nine cases had elevated P1CP or BSAP at transplant, which rapidly normalized. In most patients there was an increase in P1CP and/or BSAP several months post-transplant. In conclusion, increased osteoclast activity may be present even in apparent plateau phase of myeloma. High-dose chemotherapy with autografting may normalize abnormal bone resorption, although the effect may take several weeks to emerge and may be paralleled by increased osteoblast activity. The findings provide biochemical evidence that autografting may help normalize the abnormal bone turnover characteristic of myeloma.

scholarly journals The effects of a low-sodium base-producing diet including red meat compared with a high-carbohydrate, low-fat diet on bone turnover markers in women aged 45–75 years

2009 ◽  
Vol 102 (8) ◽  
pp. 1161-1170 ◽  
Author(s):  
Caryl A. Nowson ◽  
Annabelle Patchett ◽  
Naiyana Wattanapenpaiboon
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Dietary Intervention ◽  
Red Meat ◽  
Type I ◽  
Low Fat ◽  
Beneficial Effects ◽  
High Carbohydrate ◽  
Type I Procollagen ◽  
Acid Load

A randomised, parallel-design dietary intervention study was conducted in women (aged 45–75 years) with prehypertension or stage 1 hypertension. The aim was to compare the effects on bone turnover of a low-Na base-producing (LNAB) Dietary Approaches to Stop Hypertension (DASH)-type diet (including six serves lean red meat/week) with a high-carbohydrate low-fat (HCLF) diet with a higher acid load (both >800 mg dietary Ca/d). Fasting serum bone markers (baseline and week 14) and 24 h urinary electrolyte excretion (baseline, weeks 4, 8, 12 and 14) were measured. After the intervention period, the LNAB group (n 46) had a fall of 26 (sem 6) % (P < 0·0001) in urinary Na, an increase in K excretion (6·8 (sem 3·6) mmol/d; P = 0·07) and, compared with the HCLF group (n 49), a greater reduction in urinary Ca excretion by 0·7 (sem 0·3) mmol/d. Serum 25-hydroxyvitamin D, intact parathyroid hormone and osteocalcin did not change, and both groups had a similar increase of 23 (sem 5) % (P < 0·0001) in C-terminal telopeptide of type I collagen. The HCLF group had an 11 (sem 4) % increase (P = 0·003) in N-terminal propeptide, type I procollagen, which could indicate an increased rate of bone turnover. The fall in urinary Ca with the lower-Na lower-acid load diet is likely to have long-term beneficial effects on bone. As bone resorption was not different between the two dietary patterns with relatively high Ca intake, the effect on bone health of a dietary pattern with a lower acid load warrants further study on a lower Ca intake.

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