scholarly journals Energy Deficiency Suppresses Bone Turnover in Exercising Women With Menstrual Disturbances

2019 ◽  
Vol 104 (8) ◽  
pp. 3131-3145 ◽  
Author(s):  
Emily A Southmayd ◽  
Nancy I Williams ◽  
Rebecca J Mallinson ◽  
Mary Jane De Souza
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Reference Group ◽  
Critical Role ◽  
Type I ◽  
Mineral Density ◽  
Energy Deficiency ◽  
Exercising Women ◽  
Menstrual Disturbances

Abstract Context In exercising women, energy deficiency can disrupt the balance of bone formation and resorption, resulting in bone loss and an altered rate of bone turnover, which may influence future bone mineral density and fracture risk. Objective To assess the effects of energy status and estrogen status on bone turnover. Design Cross-sectional. Setting The Women’s Health and Exercise Laboratory at Pennsylvania State University. Participants Exercising women (n = 109) operationally defined as energy deficient or replete based on total triiodothyronine concentration and as estrogen deficient or replete based on menstrual cycle history and reproductive hormone metabolites. Main Outcome Measures Bone formation index [procollagen type I N-terminal propeptide (P1NP) concentration corrected for average P1NP concentration in healthy reference group, i.e., [P1NP]i/median [P1NP]ref], bone resorption index [serum C-terminal telopeptide (sCTx) concentration corrected for average sCTx concentration in healthy reference group, i.e., [sCTx]i/median [sCTx]ref], bone balance (ratio of bone formation index to bone resorption index to indicate which process predominates), and bone turnover rate (collective magnitude of bone formation index and bone resorption index to indicate overall amount of bone turnover). Results The combination of energy and estrogen deficiency resulted in less bone formation and a lower rate of bone turnover compared with women who were estrogen deficient but energy replete. Regardless of estrogen status, energy deficiency was associated with decreased bone resorption as well. No main effects of estrogen status were observed. Conclusions The results highlight the critical role that adequate energy plays in the regulation of bone turnover, especially bone formation, in exercising women with menstrual disturbances.

scholarly journals Bone Turnover Markers After Sleep Restriction and Circadian Disruption: A Mechanism for Sleep-Related Bone Loss in Humans

2017 ◽  
Vol 102 (10) ◽  
pp. 3722-3730 ◽  
Author(s):  
Christine M Swanson ◽  
Steven A Shea ◽  
Pamela Wolfe ◽  
Sean W Cain ◽  
Mirjam Munch ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Repeated Measures ◽  
Circadian Disruption ◽  
Sleep Restriction ◽  
Type I ◽  
Bone Biomarkers ◽  
Mineral Density ◽  
The Impact

Abstract Context Sleep abnormalities are associated with low bone mineral density. Underlying mechanisms are unknown. Objective Investigate the impact of sleep restriction with circadian disruption on bone biomarkers. Design Intervention study. Participants and Methods Four bone biomarkers [C-terminal cross-linked telopeptide of type I collagen (CTX) = bone resorption, N-terminal propeptide of type I procollagen (P1NP) = bone formation, sclerostin and fibroblast growth factor 23 = osteocyte function] were measured in bihourly serum samples over 24 hours at baseline and after ∼3 weeks of sleep restriction (5.6 hours sleep/24 hours) with concurrent circadian disruption (recurring 28-hour “day” in dim light) in 10 men (age groups: 20 to 27 years, n = 6; 55 to 65 years, n = 4). The effects of sleep/circadian disruption and age on bone biomarker levels were evaluated using maximum likelihood estimation in a mixed model for repeated measures. Results P1NP levels were lower after intervention compared with baseline (P < 0.001); the decrease in P1NP was greater for younger compared with older men (28.0% vs 18.2%, P < 0.001). There was no change in CTX (Δ = 0.03 ± 0.02 ng/mL, P = 0.10). Sclerostin levels were higher postintervention in the younger men only (Δ = 22.9% or 5.64 ± 1.10 pmol/L, P < 0.001). Conclusions These data suggest that 3 weeks of circadian disruption with concurrent sleep restriction can lead to an uncoupling of bone turnover wherein bone formation is decreased but bone resorption is unchanged. Circadian disruption and sleep restriction may be most detrimental to bone in early adulthood.

scholarly journals Novel Metabolic Pathways Associated with Serum Bone Turnover Markers in Healthy Young Adults

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 71-71
Author(s):  
Joseph Roberts ◽  
Moriah Bellissimo ◽  
Kaitlin Taibl ◽  
Karan Uppal ◽  
Dean Jones ◽  
...  
Keyword(s):  
Young Adults ◽  
Fatty Acid ◽  
Amino Acid ◽  
High Resolution ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Metabolic Pathways ◽  
Type I ◽  
Turnover Markers

Abstract Objectives Optimal bone health is maintained through a remodeling cycle consisting of resorption followed by formation. Procollagen type I N-terminal propeptide (P1NP) and C-terminal telopeptides of type I collagen (CTX) are biomarkers of bone metabolism that capture changes in bone formation and bone resorption, respectively. This study aimed to identify unique metabolic pathways related to bone turnover markers (BTMs) in healthy young adults. Methods This cross-sectional study included 34 healthy, young adults (19 females, average age 27.8 years). Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry. Fasting plasma was analyzed using dual column liquid chromatography and ultra-high-resolution mass spectrometry for metabolomics. Serum levels of P1NP and CTX were measured with ELISA. Linear regression and pathway enrichment analyses were used to identify metabolic pathways related to the BTMs. Results All participants had a normal whole-body BMD T-score. Metabolites significantly associated with P1NP (at P < 0.05) were significantly enriched in pathways linked to the TCA cycle, pyruvate metabolism, and metabolism of B-vitamins important for energy production (e.g., niacin, thiamin). Other nutrition-related metabolic pathways associated with P1NP were amino acid (proline, arginine, glutamate) and vitamin C metabolism, which are important for collagen formation. Metabolites were associated with CTX levels (at P < 0.05), which were enriched within lipid and fatty acid beta-oxidation metabolic pathways, as well as fat soluble micronutrients pathways including, vitamin D metabolism, vitamin E metabolism, and bile acid biosynthesis. Conclusions High-resolution metabolomics identified several distinct plasma metabolic pathways, including energy-yielding metabolic pathways and pathways related to fatty acid, amino acid, and micronutrient metabolism that were associated with markers of bone formation and bone resorption. Characterizing these metabolism-related pathways associated with BTMs in healthy adults is an important step towards understanding the metabolic perturbations that lead to low bone mass in older and clinical populations. Funding Sources National Institutes of Health and Emory University.

An increase in bone stability in an aripiprazole add-on or switching study

2011 ◽  
Vol 26 (S2) ◽  
pp. 1257-1257 ◽  
Author(s):  
S. Masand ◽  
R. Sherwood ◽  
K.J. Aitchison
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Partial Agonist ◽  
Bone Alkaline Phosphatase ◽  
Mental Health Disorder ◽  
Mineral Density ◽  
Open Label ◽  
Urinary Markers ◽  
Osteoblastic Activity

IntroductionSchizophrenia is a mental health disorder associated with high rates of osteoporosis. Studies have suggested antipsychotics as a major cause of accelerated decrease in bone mineral density.Oestrogen deficiency contributes to osteoporosis and causes increased osteoclast numbers/osteoclastic activity. Prolactin suppresses hypothalamo-pituitary-ovarian axis activity, leading to decreased oestrogen concentrations.Aripiprazole, an ‘atypical’ antipsychotic, is a partial agonist at dopamine D2-receptors, while other atypical antipsychotics are antagonists at these receptors. Dopamine inhibits prolactin release via these receptors at the anterior pituitary. Aripiprazole has been found to decrease prolactin concentrations in chronic schizophrenics and may be protective against osteoporosis.Quantitation of specific markers of osteoclastic (cross-linked N-telopeptide (NTX)) and osteoblastic activity (bone alkaline phosphatase (BAP)) can be correlated with bone resorption and bone formation, respectively.ObjectivesExploring whether aripiprazole is effective in stabilising bone turnover.AimsInvestigate changes in urinary markers of bone turnover.MethodsWe performed 52 week, open-label, intention-to-treat study, offering either a switch to aripiprazole or aripiprazole as add-on to initial antipsychotic medication.Serial measurements of prolactin, testosterone, 17-β-oestradiol, serum BAP, albumin, urinary creatinine, and urinary NTX concentrations were taken between 0 and 52 weeks.ResultsAt the end-point of study, versus the baseline, there were significant decreases in concentrations of urinary markers of bone resorption (P = 0.002 for NTX) and bone formation (P = .026 for BAP). Additionally, a significant decrease in prolactin (P = 0.004) and significant increase in 17-β-oestradiol concentrations (P = 0.015) were found.ConclusionsOur results show decreased overall bone turnover; and increased long-term bone stability in patients who changed medication.

Weight-bearing exercise and markers of bone turnover in female athletes

2001 ◽  
Vol 90 (2) ◽  
pp. 565-570 ◽  
Author(s):  
Dana L. Creighton ◽  
Amy L. Morgan ◽  
Debra Boardley ◽  
P. Gunnar Brolinson
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Female Athletes ◽  
Weight Bearing ◽  
Calorie Intake ◽  
Mineral Density ◽  
High Group ◽  
Markers Of Bone Turnover ◽  
Total Body

Weight-bearing activity provides an osteogenic stimulus, while effects of swimming on bone are unclear. We evaluated bone mineral density (BMD) and markers of bone turnover in female athletes ( n = 41, age 20.7 yr) comparing three impact groups, high impact (High, basketball and volleyball, n= 14), medium impact (Med, soccer and track, n = 13), and nonimpact (Non, swimming, n = 7), with sedentary age-matched controls (Con, n = 7). BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck (FN), Ward's triangle, and trochanter (TR); bone resorption estimated from urinary cross-linked N-telopeptides (NTx); and bone formation determined from serum osteocalcin. Adjusted BMD (g/cm; covariates: body mass index, weight, and calcium and calorie intake) was greater at the FN and TR in the High group (1.27 ± 0.03 and 1.05 ± 0.03) than in the Non (1.05 ± 0.04 and 0.86 ± 0.04) and Con (1.03 ± 0.05 and 0.85 ± 0.05) groups and greater at the TR in the Med group (1.01 ± 0.03) than in the Non (0.86 ± 0.04) and Con (0.85 ± 0.05) groups. Total body BMD was higher in the High group (4.9 ± 0.12) than in the Med (4.5 ± 0.12), Non (4.2 ± 0.14), and Con (4.1 ± 0.17) groups and greater in the Med group than in the Non and Con groups. Bone formation was lower in the Non group (19.8 ± 2.6) than in the High (30.6 ± 3.0) and Med (32.9 ± 1.9, P ≤ 0.05) groups. No differences in a marker of bone resorption (NTx) were noted. This indicates that women who participate in impact sports such as volleyball and basketball had higher BMDs and bone formation values than female swimmers.

scholarly journals Low Dose Estrogen and Calcium Have an Additive Effect on Bone Resorption in Older Women1

1999 ◽  
Vol 84 (1) ◽  
pp. 179-183
Author(s):  
K. M. Prestwood ◽  
D. L. Thompson ◽  
A. M. Kenny ◽  
M. J. Seibel ◽  
C. C. Pilbeam ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Older Women ◽  
Low Dose ◽  
Type I Collagen ◽  
Control Group ◽  
Type I ◽  
Markers Of Bone Formation ◽  
Markers Of Bone Resorption

Previous studies have shown that treatment with estrogen or calcium decreases bone turnover in older women. The mechanisms by which estrogen and calcium exert their effects are probably different. We therefore examined the possibility of an additive or synergistic effect of combined treatment with calcium and low dose estrogen on bone turnover in older women, using biochemical markers. Thirty-one healthy women over 70 yr of age were randomized to 12 weeks of treatment with either micronized 17β-estradiol [0.5 mg/day Estrace (E2)] or 1500 mg/day elemental calcium, given as carbonate plus vitamin D (800 IU/day; Ca+D). At the end of the initial 12-week treatment period, both groups received both Ca+D and E2 for an additional 12 weeks. Eleven older women were followed for 36 weeks without any treatment and served as a control group. Serum and urine were collected at baseline, at 12 and 24 weeks on treatment, and at 12 weeks after treatment was terminated for measurement of biochemical markers of bone turnover. Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I procollagen peptide; markers of bone resorption were urinary cross-linked C-telopeptides and N-telopeptides of type I collagen, serum cross-linked N-telopeptides of type I collagen, urinary free deoxypyridinoline cross-links, and serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in bone turnover measures over time by group. All markers of bone resorption decreased with initial treatment and decreased further with combination therapy (P < 0.001). Markers of bone formation decreased with Ca+D treatment, but not with E2 alone; there was no additional effect of combination therapy on formation markers compared to Ca+D alone. Neither markers of formation nor resorption changed in the control group. These results suggest that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation, in older women. Thus, the combination of low dose estrogen plus calcium is likely to be more effective in older women than either treatment alone.

scholarly journals Effects of the Circadian Variation in Serum Cortisol on Markers of Bone Turnover and Calcium Homeostasis in Normal Postmenopausal Women1

1998 ◽  
Vol 83 (3) ◽  
pp. 751-756 ◽  
Author(s):  
Hassan M. Heshmati ◽  
B. Lawrence Riggs ◽  
Mary F. Burritt ◽  
Carol A. McAlister ◽  
Peter C. Wollan ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I Collagen ◽  
Serum Cortisol ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Type I ◽  
Serum Osteocalcin ◽  
Circadian Pattern

Bone turnover has a circadian pattern, with bone resorption and, to a lesser extent, bone formation increasing at night. Serum cortisol also has a circadian pattern and is a potential candidate for mediating the circadian changes in bone turnover. Thus, we measured bone formation and resorption markers before (study A) and after (study B) elimination of the morning peak of cortisol. We also assessed effects of the circadian cortisol pattern on serum calcium, PTH, and urinary calcium excretion. Ten normal postmenopausal women, aged 63–75 yr (mean, 69 yr), were studied. Metyrapone was administered to block endogenous cortisol synthesis and either a variable (study A) or a constant (study B) infusion of cortisol was given to reproduce and then abolish the morning cortisol peak. Blood was sampled every 2 h for serum cortisol, ionized calcium, PTH, and bone formation markers[ osteocalcin and carboxyl-terminal propeptide of type I collagen (PICP)], and timed 4-h urine samples were collected for measurement of calcium, phosphorus, sodium, potassium, and bone resorption markers (N-telopeptide of type I collagen and free deoxypyridinoline). During study A, serum osteocalcin had a circadian pattern, with a peak at 0400 h and a nadir at 1400 h. During study B, however, the afternoon nadir of serum osteocalcin was eliminated (P < 0.001 and P < 0.005 for the difference in the patterns of peak and nadir, respectively, on the 2 study days). In contrast, the circadian patterns of serum PICP and urinary N-telopeptide of type I collagen and free deoxypyridinoline were virtually identical during the two studies. Urinary calcium excretion declined after the cortisol peak, without differences between the 2 study days in phosphorus or sodium excretion or in serum PTH. We conclude that the circadian variation in serum cortisol is responsible for the circadian pattern of serum osteocalcin, but not that of PICP or bone resorption markers. The physiological variation in serum cortisol may also reduce urinary calcium excretion.

scholarly journals Serum Osteoprotegerin as a Determinant of Bone Metabolism in a Longitudinal Study of Human Pregnancy and Lactation

2003 ◽  
Vol 88 (11) ◽  
pp. 5361-5365 ◽  
Author(s):  
K. E. Naylor ◽  
A. Rogers ◽  
R. B. Fraser ◽  
V. Hall ◽  
R. Eastell ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Bone Resorption ◽  
Bone Turnover ◽  
Type I Collagen ◽  
Human Breast Milk ◽  
Type I ◽  
Mineral Density ◽  
Human Pregnancy ◽  
Pregnancy And Lactation ◽  
In Pregnancy

Abstract Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor κB ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20–36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum β C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 ± 16% (mean ± sem) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum β C-terminal telopeptides by 76 ± 17%; urinary N-terminal telopeptides by 219 ± 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 ± 58 ng/ml in milk vs. 0.42 ± 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.

scholarly journals Capture the fracture - use of bone turnover markers in clinical practice

2016 ◽  
Vol 144 (7-8) ◽  
pp. 450-455
Author(s):  
Miljanka Vuksanovic ◽  
Teodora Beljic-Zivkovic
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Remodeling ◽  
Bone Turnover Markers ◽  
Bone Markers ◽  
Living Tissue ◽  
Mineral Density ◽  
Turnover Markers ◽  
Markers Of Bone Formation

Bone is a living tissue, metabolically very active, with the level of turnover of about 10% per year. Bone remodeling is a well-balanced process of bone resorption, induced by osteoclasts and bone formation maintained osteoblasts. Loss of bone remodeling balance, with increased bone resorption, leads to osteoporosis. Bone turnover markers are classified as markers of bone formation and of bone resorption. During the growth and development of skeleton, bone turnover markers show higher levels of activity than in the adult period. The increase in biochemical markers peaks again in the postmenopausal period, indicating accelerated bone remodeling. Bone mineral density is an important predictor of an osteoporotic fracture. Timely assessment of risk factors of osteoporosis and bone markers can detect subjects with accelerated bone remodeling and osteoporosis. This may introduce adequate therapy and prevent fracture.

Romosozumab and Sequential Therapy in Postmenopausal Osteoporosis

2020 ◽  
Vol 35 (7) ◽  
pp. 297-308
Author(s):  
Rachel M. Slaton ◽  
Katie Boyd ◽  
Maryam Iranikhah
Keyword(s):  
Bone Mineral Density ◽  
Clinical Trials ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Sequential Therapy ◽  
Controlled Clinical Trials ◽  
Mineral Density ◽  
Turnover Markers

OBJECTIVE: To review and summarize studies on the effects of romosozumab as sequential therapy for improvements in bone turnover markers, bone mineral density (BMD), and clinical fracture in postmenopausal (PMP) women.<br/> DATA SOURCES: A search of PubMed (1966-August 2019) and International Pharmaceutical Abstracts (1970-August 2019) was conducted using the MeSH and key word term romosozumab and limited to controlled clinical trials.<br/> STUDY SELECTION AND DATA EXTRACTION: An initial review yielded 12 articles. Articles that did not evaluate use of romosozumab before or after another osteoporosis treatment were excluded. Five articles that evaluated the effects of sequential treatment with romosozumab in PMP women on bone turnover markers, bone mineral density, and fracture were included in the final review.<br/> DATA SYNTHESIS: Romosozumab is a humanized, monoclonal antibody that increases bone formation and reduces bone resorption via inhibition of sclerostin. This inhibition stimulates signaling pathways resulting in increased bone formation, reduced bone resorption and increases in BMD. Romosozumab is indicated for the treatment of osteoporosis in PMP women who are at high risk for fracture and failed or cannot take other treatments. The current evidence describing the controlled clinical trials that evaluated use of romosozumab in sequence with other therapies for treatment of PMP osteoporosis is summarized.<br/> CONCLUSION: An evaluation of studies where romosozumab was used in sequence to other therapies in PMP women showed that it causes significant reductions in bone resorption markers, increases in bone-formation markers, improves BMD, and reduces the risk of clinical fracture. However, these efficacy improvements must be carefully weighed against the increased risk of cardiovascular adverse effects compared with other treatments.

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