scholarly journals Biochemical Bone Turnover Markers and Osteoporosis in Older Men: Where Are We?

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Pawel Szulc

In men aged less than 60, the association of serum and urinary levels of biochemical bone turnover markers (BTMs) and bone mineral density (BMD) is weak or not significant. After this age, higher BTM levels are correlated weakly, but significantly, with lower BMD and faster bone loss. Limited data from the cohort studies suggest that BTM measurement does not improve the prediction of fragility fractures in older men in comparison with age, BMD, history of falls and fragility fractures. Testosterone replacement therapy (TRT) decreases bone resorption. During TRT, bone formation markers slightly increase (direct effect on osteoblasts), then decrease (slowdown of bone turnover). Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate) induce a rapid decrease in bone resorption followed by a milder decrease in bone formation. In men receiving antiresorptive therapy for prostate cancer, zoledronate, denosumab and toremifene decrease significantly levels of bone resorption and bone formation markers. Teriparatide induced a rapid increase in serum concentrations of bone formation markers followed by an increase in bone resorption. We need more studies on the utility of BTM measurement for the improvement of the persistence and adherence to the anti-osteoporotic treatment in men.

2016 ◽  
Vol 144 (7-8) ◽  
pp. 450-455
Author(s):  
Miljanka Vuksanovic ◽  
Teodora Beljic-Zivkovic

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.


2020 ◽  
Vol 35 (7) ◽  
pp. 297-308
Author(s):  
Rachel M. Slaton ◽  
Katie Boyd ◽  
Maryam Iranikhah

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.


2020 ◽  
Vol 35 (7) ◽  
pp. 297-308
Author(s):  
Rachel M. Slaton ◽  
Katie Boyd ◽  
Maryam Iranikhah

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.


Lupus ◽  
2021 ◽  
Vol 30 (6) ◽  
pp. 965-971
Author(s):  
Wang Tianle ◽  
Zhang Yingying ◽  
Hong Baojian ◽  
Gu Juanfang ◽  
Wang Hongzhi ◽  
...  

Objectives SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. Methods A total of 865 female subjects were recruited from Zhejiang Provincial People’s Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of β - I collagen (β-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. Results In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and β-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of β-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, β-CTX reached a high value in summer and PINP reached a low value in winter. Conclusion The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.


2011 ◽  
Vol 71 (1) ◽  
pp. 71-74 ◽  
Author(s):  
L Senolt ◽  
H Hulejova ◽  
O Krystufkova ◽  
S Forejtova ◽  
L Andres Cerezo ◽  
...  

ObjectiveDickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and its lower levels are linked to new bone formation. The aim of this study was therefore to explore serum levels of DKK-1 and to evaluate DKK-1's association with the severity of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH).MethodsSerum levels of total and functional DKK-1 and C-reactive protein (CRP) were measured in 37 patients with DISH and 22 healthy age and sex-matched controls. Plain radiographs of the cervical and thoracic spine were performed, and the diagnosis of DISH was defined using the Resnick criteria. Patients were divided into three groups based on spinal involvement. Bone mineral density (BMD) and bone turnover markers were evaluated in patients with DISH.ResultsThe levels of total serum DKK-1 were significantly lower in patients with DISH than in healthy controls (p<0.0001). Importantly, low serum levels of DKK-1 were associated with more severe spinal involvement in DISH, independent of age, sex, disease duration, CRP, bone turnover markers or BMD. However, these findings were less significant for functional DKK-1.ConclusionThese observations indicate that DKK-1 may play a significant role in bone formation during DISH.


2019 ◽  
Vol 105 (4) ◽  
pp. e1536-e1548 ◽  
Author(s):  
Laurent Maïmoun ◽  
Patrick Garnero ◽  
Thibault Mura ◽  
David Nocca ◽  
Patrick Lefebvre ◽  
...  

Abstract Objective The threefold aim was to (1) compare areal bone mineral density (aBMD), bone turnover markers, and periostin levels in young women with either anorexia nervosa (AN) or obesity (OB) and controls (CON); (2) model the profiles according to age; and (3) determine the parameters associated with aBMD. Subjects and Methods One hundred and fifty-two young women with ages ranging from 16.0 to 27.0 years were subdivided into 3 groups (AN, OB, CON). The CON group was age-matched by ±6 months. aBMD, bone turnover markers, and periostin levels were evaluated. Results aBMD modeling showed that hip aBMD was higher in OB than in the other 2 groups from 19 years, and AN presented lower values than CON from 21 years. aBMD at the lumbar spine was higher in older OB and CON women, starting from 20 to 22 years, but in AN the difference with the other 2 groups increased with age. Periostin levels were lower in OB than in AN or CON, but no variation with age was observed. Compared with controls, OB and AN presented similarly lower markers of bone formation, although markers of bone resorption were lower in OB and higher in AN. A modeling approach showed that markers of bone formation and resorption were lower in older than in younger CON, whereas the values of these bone markers remained relatively constant in AN and OB. In all groups, lean body mass (LBM) was the parameter most positively correlated with aBMD. Conclusion This study demonstrated that weight extremes (AN or OB) influence aBMD, bone remodeling and periostin profiles. Moreover, factors related to aBMD were specific to each condition, but LBM was the parameter most consistently associated with aBMD.


Aging ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 19539-19545
Author(s):  
Aleksandra Rył ◽  
Iwona Rotter ◽  
Aleksandra Szylińska ◽  
Alina Jurewicz ◽  
Andrzej Bohatyrewicz ◽  
...  

2020 ◽  
Author(s):  
Rosemary Dineen ◽  
Lucy-Ann Behan ◽  
Grainne Kelleher ◽  
Mark J Hannon ◽  
Jennifer J Brady ◽  
...  

Abstract Background: Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group.Methods: Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-hour serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-hour urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS).Results: Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20mg/10mg) [670.5 (IQR 621-809.2)] compared to those on dose C (10mg/5mg) [562.8 (IQR 520.1-619.6), p=0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC[1-49] (r=-0.42, p=0.03), and PINP (r=-0.49, p=0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC[1-49] (r=-0.41, p=0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r=-0.39, p=0.04), and OC[1-49] (r=-0.35, p=0.06).Conclusion: Serum cortisol and cortisone and total urinary corticosteroid metabolites are associated with alterations in bone turnover markers even at replacement doses of hydrocortisone suggesting a potentially negative role of tissue-specific metabolism of glucocorticoids on bone metabolism in patients receiving hydrocortisone replacement therapy.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Rosemary Dineen ◽  
Lucy-Ann Behan ◽  
Grainne Kelleher ◽  
Mark J. Hannon ◽  
Jennifer J. Brady ◽  
...  

Abstract Background Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. Methods Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). Results Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621–809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1–619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1–49] (r = − 0.42, p = 0.03), and PINP (r = − 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1–49] (r = − 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r = − 0.39, p = 0.04), and OC [1–49] (r = − 0.35, p = 0.06). Conclusion Serum cortisol and cortisone and total urinary corticosteroid metabolites are negatively associated with bone turnover markers in patients receiving replacement doses of hydrocortisone, with nocturnal glucocorticoid exposure having a potentially greater influence on bone turnover. Trial registration Irish Medicines Board Clinical Trial Number – CT900/459/1 and EudraCT Number – 2007-005018-37. Registration date: 07-09-2007.


2020 ◽  
Vol 106 (1) ◽  
pp. e171-e181
Author(s):  
Arthi Thirumalai ◽  
Fiona Yuen ◽  
John K Amory ◽  
Andrew N Hoofnagle ◽  
Ronald S Swerdloff ◽  
...  

Abstract Context Dimethandrolone undecanoate (DMAU) is being developed as a male contraceptive. Daily oral administration of DMAU, a potent androgen that is not aromatized, markedly suppresses serum testosterone (T) and estradiol (E2) in healthy men. E2 deficiency can increase bone resorption in men. Objective This work aimed to assess changes in bone turnover markers with DMAU administration in a 28-day study. Design A randomized, double-blind, placebo-controlled study was conducted. Setting This study took place at 2 academic medical centers. Participants Healthy men, age 18 to50 years (n = 81), participated. Intervention Men received 0, 100, 200, or 400 mg of oral DMAU for 28 days. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and procollagen type I amino-terminal propeptide (P1NP; bone formation marker) were measured on days 1 and 28. Main Outcome Measures Changes in bone turnover markers and serum hormones over the treatment period were measured. Results On day 28, median serum T and E2 were markedly suppressed in all treatment groups vs placebo (P &lt; .001 for both). Percentage change (%) in serum P1NP significantly differed across treatment groups (P = .007): Serum P1NP significantly increased in the 200 mg (5%, interquartile range [IQR] –7% to 27%) and 400 mg (22%, IQR –1% to 40%) groups relative to placebo (–8%, IQR –20% to 0%). Change (%) in serum CTX did not differ between groups (P = .09). Conclusions DMAU administration for 28 days to healthy men leads to marked suppression of serum T and E2, yet increases P1NP, a serum marker of bone formation. Longer-term studies of the potent androgen DMAU are warranted to determine its impact on bone health in men.


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