Biomarkers Of Bone Metabolism Research Articles

Bone structure and function in male C57BL/6 mice: Effects of a high-fat Western-style diet with or without trace minerals

PurposeOsteoporosis occurs in both women and men, but most of what we know about the condition comes from studies in females. The present study examined bone structure and function over an 18-month period in male C57BL/6 mice maintained on either a rodent chow diet (AIN76A) or a high-fat, Western-style diet (HFWD). Effects of mineral supplementation were assessed in both diets. MethodsTrabecular and cortical bone structure in femora and vertebrae were assessed by micro-CT analysis. Following this, bone stiffness and strength measurements were made. Finally, bone levels of several cationic trace elements were quantified, and serum biomarkers of bone metabolism evaluated. ResultsBone loss occurred over time in both diets but was more rapid and extensive in mice on the HFWD. Dietary mineral supplementation reduced bone loss in both diets and increased bone stiffness in the femora and bone stiffness and strength in the vertebrae. Bone content of strontium was increased in response to mineral supplementation in both diets. ConclusionsBone loss was more severe in mice on the HFWD and mineral supplementation mitigated the effects of the HFWD. In comparison to previous findings with female C57BL/6 mice, the present studies indicate that males are more sensitive to diet and benefited from a healthy diet (AIN76A), while females lost as much bone on the healthy diet as on the HFWD. Male mice benefited from mineral supplementation, just as females did in the previous study.

A Glance at Biomarkers of Bone Metabolism

A Glance at Biomarkers of Bone Metabolism

Bone Disease in Myeloma: The Claws of CRAB.

A dynamic approach to use bisphosphonates according to biomarkers of bone metabolism is presented in the Z-MARK study by Raje and colleagues. This is a major step forward toward a rational approach to bisphosphonate usage.

The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women.

BackgroundRecent studies have linked non-alcoholic fatty liver disease (NAFLD) to a reduced bone mineral density (BMD). We aimed to detect the quantitative association of liver fat content (LFC) and serum alanine aminotransferase (ALT) with BMD in a middle-aged and elderly Chinese population.MethodsThe lumbar spine, hip and whole body BMDs were measured using dual-energy x-ray absorptiometry (Lunar iDXA, GE Healthcare) in 1659 Chinese (755 men and 1028 postmenopausal women) from Shanghai Changfeng community. Liver fat content was quantified via an ultrasound quantitative method. Multivariate linear regression analyses were carried out to determine the independent association of LFC and serum ALT with BMD and bone metabolic biomarkers. We also attempted to investigate the synergistic association between LFC and ALT as risk factors for bone mineral loss in Chinese.ResultsSubjects with higher LFC had significantly lower BMD at all skeletal sites. Univariate correlation analysis showed that both LFC and ALT were inversely associated with BMD at the spine (r = −0.116, P < 0.001 and r = −0.102, P = 0.005), hip (r = −0.095, P = 0.014 and r = −0.075, P = 0.041) and whole body sites (r = −0.134, P < 0.001 and r = −0.164, P < 0.001) in men. After confounders were controlled for, LFC and ALT remained associated with BMD and bone formation biomarkers in men, but not postmenopausal women. When both NAFLD and elevation of ALT were present, there was a significant synergistic worsening of the BMDs at all bone sites.ConclusionsLiver fat content and serum ALT were inversely correlated with BMD in middle-aged and elderly men. The underlying mechanism might relate to a reduction in osteoblast activity. Elevation of the hepatotoxic biomarker ALT may indicate high risk for osteoporosis in patients with NAFLD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0766-3) contains supplementary material, which is available to authorized users.

Relationship between Bone Mineral Density and Metabolic Biomarkers in Postmenopausal Women who Underwent a Comprehensive Health Check-up

Relationship between Bone Mineral Density and Metabolic Biomarkers in Postmenopausal Women who Underwent a Comprehensive Health Check-up

Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis.

Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p < 0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p < 0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p < 0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p < 0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.

Contribution of Musculoskeletal Disorders to Chronic Lumbago in Parkinson’s Disease

Purpose: To clarify the impact of bone metabolism disorder on lumbago in Parkinson’s Disease (PD). Methods: Data was retrospectively analyzed from 52 patients with PD in our outpatient clinic for more than 1 year (mean age, 63 ± 4 years old; mean duration from onset, 6.3 ± 0.8 years). Patients’ characteristics, comorbid musculoskeletal disorders, serum bone metabolism biomarkers, and bone mineral density were examined. Results: Twenty-one PD patients (40.2%) had chronic lumbago. Severe comptocormia and scoliosis were the most common musculosketal disorders in this group (47.6%) affected by lumbago, followed by osteoporosis (14.3%), compression fracture (4.8%). There was no significant difference in the duration of PD, body mass index, frequency of falls, bone mineral density, tartrate-resistant acid phosphatase-5b, osteocalcin, and N-terminal telopeptide between PD patients with or without chronic lumbago. Multivaritae logistic regression analysis identified the independent predictors of chroni lumbago in PD patients as Hoen-Yahr stage (odds ration [OR] = 2.794, 95%CI 1.103 - 7.076), and elevated serum 1,25-OH2 vitamin D level ([OR] = 0.92, 95%CI 0.86 - 98). Conclusion: Bone metabolism disorders are found to be associated with chronic lumbago in PD patients.

Osteopontin and osteoprotegerin levels in type 2 diabetes and their association with cardiovascular autonomic function

AimsOsteopontin (OPN) and osteoprotegerin (OPG) are bone metabolism biomarkers potentially associated with nerve function. We evaluated the association of cardiovascular autonomic nerve function, OPN, and OPG in 50 individuals with type 2 diabetes mellitus (T2DM). MethodsRR-variation during deep breathing (i.e., mean circular resultant (MCR) and expiration/inspiration (E/I) ratio) was used to assess parasympathetic nerve function. Participants’ demographics, HbA1c, 25-hydroxyvitamin D (25(OH)D), BMI, HOMA-IR, calcium, parathyroid hormone, creatinine, OPN, and OPG were determined. ResultsUsing stepwise multiple linear regression analysis with MCR or E/I ratio as the dependent variable, OPN was independently associated with reduced autonomic function. A previous report showed a significant association of cardiovascular autonomic function with age, 25(OH)D insufficiency, and the interaction of age×25(OH)D insufficiency. Here we report a novel association for OPN and its interaction with age indicating that for those who are younger, elevated OPN levels are related to a greater loss of autonomic function (MCR model R2=0.598, p<0.001; E/I model R2=0.594, p<0.001). ConclusionOur results suggest that OPN is associated with reduced parasympathetic function, particularly in younger individuals with T2DM. Further studies are needed to determine if OPN is neuroprotective, involved in the pathogenesis of autonomic dysfunction, or a bystander.

Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model

Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2μg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture.

Randomized, Double-blind, Placebo-controlled Trial of the Effects of Polycan, β-glucan Originating from Aureobasidium Pullulans, on Bone Biomarkers in Healthy Women

Polycan originating from Aureobasidium pullulans is mostly composed of β-1, 3/1, 6 glucans and possesses an anti-osteoporotic effect. We conducted a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of the polycan on bone biochemical markers in healthy perimenopausal women. Sixty subjects were randomly allocated to 2 groups?group 1 received 400 mg of polycan and group 2 received placebo?these were administered once daily for 28 days. Fasting blood and urine samples were collected at baseline and 4 weeks after treatment. The primary outcome was change in osteocalcin (OSC) and bone-specific alkaline phosphatase (BALP). Changes in calcium (Ca), phosphorus (P), C-telopeptide of collagen cross-links (CTx), N-telopeptide of collagen cross-links (NTx), and deoxypyridinoline (DPYR) were the secondary outcomes. A safety assessment was performed using adverse event (AE) and laboratory data. After 4 weeks of polycan treatment, OSC, DPYR, and BALP levels changed (P 0.05) significantly from baseline in both groups. However, no significant differences were observed in any markers between the 2 groups, except for P (P 0.05). Interestingly, group 2 showed a significant increase in CTx (65.2%, P 0.05), while CTx in group 1 slightly increased (17.2%). Both groups showed no significant differences in AE. Although 4 weeks of polycan treatment did not have a statistically significant effect on bone metabolism biomarkers, increases in CTx were modestly inhibited by polycan. Further studies in a large population and longer treatment periods are needed to confirm the effect of polycan on bone turnover.

Osteoprotective Effect of Echinocystic Acid, a Triterpone Component from Eclipta prostrata, in Ovariectomy-Induced Osteoporotic Rats.

Echinocystic acid (EA) is a natural triterpone enriched in various herbs and has been used for medicinal purposes in China. In the present study, we systematically examined the effects of EA on ovariectomy-induced osteoporosis in rats for the first time. Three-month-old female ovariectomy (OVX) Sprague–Dawley rats were used to evaluate the osteoprotective effect of EA. Results showed that administration of EA (5 or 15 mg/kg/day) for 12 weeks prevented lower levels of maximum stress and Young’s modulus of femur induced by OVX. EA also recovered bone metabolic biomarkers levels in OVX rats, including osteocalcin, alkaline phosphatese, deoxypyridinoline, and urinary calcium and phosphorus. EA (5 and 15 mg/kg/day) could prevent the alteration of total bone mineral density in the femur caused by OVX. However, only high dose (15 mg/kg/day) of EA significantly improved trabecular architecture, as evidenced by higher levels of bone volume/tissue volume, trabecula number, and trabecula thickness, and lower levels of trabecula separation and structure model index compared with OVX rats. In addition, EA treatment decresed the serum levels of IL-1β and TNF-α in OVX rats. In conclusion, EA could prevent reduction of bone mass and strength and improve the cancellous bone structure and biochemical properties in OVX rats. Hence, EA may serve as a new candidate or a leading compound for anti-osteoporosis.

Association between basal metabolic function and bone metabolism in postmenopausal women with type 2 diabetes

ObjectiveDiabetes is a risk factor for osteoporosis, and glycemic control is critical during osteoporosis treatment in patients with type 2 diabetes (T2D). However, diabetic therapies have potentially adverse effects on bone metabolism. Additionally, biomarkers for bone metabolism are directly affected by drug therapies for osteoporosis. This study examined resting energy expenditure (REE) and respiratory quotient (RQ) as indices of bone metabolism in postmenopausal Japanese women with T2D. MethodsForty-six postmenopausal Japanese women with T2D were examined. Procollagen type 1 N-terminal propeptide (P1NP, a fasting serum bone formation marker) and carboxy-terminal collagen cross-links-1 (CTX-1, a resorption marker) were evaluated, along with intact parathyroid hormone, 25-hydroxyvitamin D (25[OH]D), urine microalbumin, motor nerve conduction velocity, sensory nerve conduction velocity, R-R interval, body composition, REE, RQ, and bone mineral density at the nondominant distal radius. ResultsThe mean T-score was low with high variance (−1.7 ± 1.6), and 18 patients (39%) met the criteria for osteoporosis. REE was positively correlated with body mass index (β = 0.517; r2 = 0.250), serum calcium (β = 0.624; r2 = 0.200), glycated hemoglobin A1C for the previous 6 mo (β = 0.395; r2 = 0.137), and the serum P1NP/CTX-1 ratio (β = 0.380; r2 = 0.144). RQ was positively correlated with serum 25(OH)D (β = 0.387; r2 = 0.131). ConclusionThe basal metabolic rate and diabetic pathophysiology are interrelated with bone turnover.

Hemorrhage trauma increases radiation-induced trabecular bone loss and marrow cell depletion in mice.

Exposure to high-dose radiation results in deleterious effects on skeletal tissue. However, the effects of combined trauma such as radiation and hemorrhage on skeletal properties have yet to be elucidated. The purpose of this study was to evaluate the effects of radiation injury combined with hemorrhage on trabecular bone properties and biomarkers of bone metabolism, and to determine whether hemorrhage enhances radiation-associated bone loss. Male CD2F1 mice (10 weeks old) were exposed to one single dose of gamma radiation ((60)Co): 0 or 7.25 Gy. Two hours after irradiation, animals were bled 0% (n = 8) or 20% (n = 8) of total blood volume via the submandibular vein. Mice were euthanized 30 days after irradiation, and distal femora were analyzed using standard histomorphometry to determine changes in trabecular bone volume (BV/TV), thickness (Tb.Th), spacing (Tb.Sp), number (Tb.N) and marrow adipocyte density. Femurs from mice euthanized 1, 7 and 15 days post injury were flushed and total bone marrow cells were counted. Radiation exposure resulted in deleterious effects on distal femur BV/TV (-63%), Tb.Th (-34%), Tb.N (-45%), Tb.Sp (+125%) and adipocyte density (+286%) compared with the sham-irradiated mice (0 Gy; P < 0.05). Hemorrhage after irradiation resulted in greater deleterious effects on the distal femur with BV/TV (-13%), Tb.Th (-44%), Tb.N (-26%), Tb.Sp (+29%) and marrow adipocyte density (+33%) compared with radiation exposure only (P < 0.05). Analysis of the biomarkers of bone metabolism in serum from irradiated and hemorrhaged mice revealed significantly lower levels of osteocalcin (-60%) and procollagen type 1 amino-terminal propeptide (-36%; P1NP, biomarkers of bone formation activity), as well as elevations in sclerostin (+56%; SOST, an inhibitor of bone formation) compared with serum from irradiated only mice (P < 0.05). Additionally, the onset of bone marrow cell depletion in irradiated and hemorrhaged mice occurred earlier and to a greater extent compared to that in irradiated only mice. This study provides definitive, preliminary evidence that hemorrhage further exacerbates trabecular bone loss associated with nonlethal high-dose gamma radiation.

Relationship of Bone Metabolism Biomarkers and Periodontal Disease: The Osteoporotic Fractures in Men (MrOS) Study.

Periodontitis is an inflammatory disease of tooth-supporting tissue leading to bone destruction and tooth loss. Periodontitis affects almost 50% of adults greater than 30 years of age. This study evaluated the association between biomarkers linked to bone formation and resorption with the occurrence and progression of periodontal disease in older men (≥ 65 y). The Osteoporotic Fractures in Men (MrOS) study is a prospective, observational study among men 65 years of age and older. This ancillary study, Oral and Skeletal Bone Loss in Older Men, was conducted at two of the six MrOS study sites (Birmingham, AL and Portland, OR). Patients underwent medical and dental evaluation. Diagnoses of periodontitis were based on clinical attachment loss, pocket depth, calculus, plaque, and bleeding on a random half-mouth. Bone metabolism biomarkers included serum levels of calcium, phosphate (Pi), alkaline phosphatase, albumin, carboxy-terminal collagen crosslinks (CTX), N-terminal propeptides of type I procollagen, isoform 5b of tartrate-resistant acid phosphatase, and urine alpha- carboxy-terminal collagen crosslinks (alpha-CTX) and beta-CTX and serum levels of calciotropic hormones vitamin D (25(OH)D) and PTH. The aim of this study is to correlate bone metabolism biomarkers with prevalence and progression of periodontal disease in older men. Patients with more severe periodontitis had significantly higher levels of PTH (P trend = .0004), whereas 25(OH)D was lower (P trend = .001). In a subset of men reevaluated at a second dental visit, improvement of periodontitis was associated with lower alpha-CTX, beta-CTX, and CTX levels at baseline after adjusting for age, site, and body mass index. This study suggests that a distinct set of biomarkers of bone metabolism are associated with more severe periodontal disease (PTH, 25(OH)D) and periodontal progression (alpha-CTX, beta-CTX, and CTX) over time.

Joint incongruity and biomarkers of bone metabolism as predictors of post-traumatic arthritis in mice

Joint incongruity and biomarkers of bone metabolism as predictors of post-traumatic arthritis in mice

Identification of a novel target, FoxA2, in the onset and development of osteoarthritis

Identification of a novel target, FoxA2, in the onset and development of osteoarthritis

Effect of calcitriol supplementation and tail suspension on serum biomarkers of bone formation in rats.

BackgroundCalcitriol is documented to cause significant increase in bone mass densitometry counteracting osteoporosis. Promising results of calcitriol supplementation in studies aiming space flight induced osteoporosis is little and the effect of this hormone on biomarkers of bone metabolism is not examined yet in space flight models of osteoporosis in rats.MethodsThis was an interventional animal study being performed in a 1-month period. We included 21 Sprague Dawley strain rats (>200 gr, >6 week) who were randomly assigned to receive daily supplementation of oral 0.03μgr calcitriol and to be submitted to tail suspension model. Rats were followed for 1 month and were tested for serum osteocalcin (OC), alkaline phosphatase (ALP) and serum calcium at the beginning and the end of the study period. The results were analyzed and compared between groups.ResultsAlthough serum levels of osteocalcin and alkaline phosphatase biomarkers and total serum calcium were not significantly different within and between study groups, their levels were increased in tail suspension model compared to control group. The levels of these biomarkers were lower in those who were submitted to tail suspension model and received calcitriol supplementation compared to those who were only submitted to tail suspension (60.14 ± 11.73 ng/mL vs. 58.29 ± 2.69 ng/mL; p = 0.696 for osteocalcin and 381.86 ± 99.16 mU/mL vs. 362.57 ± 27.41 ng/mL; p = 0.635 for alkaline phosphatase).ConclusionSupplementation of daily diet with calcitriol in rats under weightlessness conditions may results in lower values for bone metabolic biomarkers of alkaline phosphatase and osteocalcin and serum calcium. This pattern of change in biomarkers of bone formation, may point to the capacity of calcitriol supplementation in preventing cellular process of osteoporosis. Thus calcitriol supplementation could be an available, economic and effective strategy for preventing bone metabolic changes related to weightlessness commonly encountered in space flight. The outcome of this study needs to be further studied in future trying to find more definite results.

Bone metabolism biomarkers in men with advanced prostate cancer (PC) and bone metastases treated with denosumab versus zoledronic acid (ZA).

267 Background: Denosumab, compared with ZA, has recently demonstrated significant benefits in preventing skeletal-related events (SREs) in a double-blind phase 3 study of men with castration-resistant PC and bone metastases (N=1901). This post hoc analysis was performed to determine if key bone metabolism biomarker levels correlated with time-to-first SRE. Methods: Time-to-Grade ≥2 increase in total serum alkaline phosphatase (ALP) was assessed for correlation with time-to-first SRE. Levels of urinary N-telopeptide (uNTX) and serum bone-specific alkaline phosphatase (BSAP) markers were measured at baseline and study week 13, and correlations with time-to-first SRE were assessed. Covariate analyses were performed using a Cox proportional hazards model, stratified by treatment group or (for baseline analyses) with treatment group as the independent variable. Results: Analysis of the relationship between time-to-Grade ≥2 increase in total ALP and time-to-first SRE demonstrated that Grade ≥2 increases in ALP of PC patients were associated with a higher risk of first SRE (hazard ratio [HR] 1.838, 95% confidence interval [CI] 1.559, 2.167; P&lt;0.0001). In dichotomized analyses (&lt; vs ≥ median), a higher level of uNTX and BSAP (at baseline or week 13) was correlated with an increased risk of first SRE (Table). In baseline covariate analyses, treatment benefit for denosumab was maintained after adjusting for either baseline uNTX (HR 0.818, 95% CI 0.703, 0.951; P=0.0091) or BSAP (HR 0.813, 95% CI 0.700, 0.943; P=0.0061). Conclusions: Higher levels of uNTX or BSAP at baseline or week 13 were associated with worse SRE outcomes in men with advanced PC and bone metastases. Denosumab was more efficacious for preventing or delaying SREs compared with ZA, regardless of bone-related biomarker levels. Relationship of covariate to time-to-first SRE Clinical trial information: NCT00321620. [Table: see text]

The generation of C-3α epimer of 25-hydroxyvitamin D and its biological effects on bone mineral density in adult rodents.

The source and function of C-3α epimer of 25(OH)D (C-3 epimer) is unknown. The objectives were to (1) establish if increasing doses of vitamin D (VD) results in a proportionate dose-response in C-3 epimer; and (2) determine the biological response of bone to C-3 epimer treatment. Sprague Dawley rats (12 weeks, n = 36 female, n = 36 male) were randomized to control AIN93-M diet (1 IU VD3/g diet) or an experimental diet for 8 weeks containing VD3 at 2 or 4 IU/g diet, C-3 epimer at 0.5 or 1 IU/g diet or 25(OH)D (0.5 IU/g diet). BW and food consumption were measured weekly. Blood was sampled at week 0, 4, and 8 for assessment of VD metabolites and bone metabolism biomarkers. DXA (week 0, 4, and 8) and in vivo micro CT (μCT) (week 0 and 8) were performed in vivo plus ex vivo μCT imaging and bone biomechanics. Dietary intake and anthropometry did not differ among diet groups. The dose-response of VD generated significantly elevated C-3 epimer only in females with concentrations of 4 IU VD diet group [mean 84.6 (62.5) nmol/L] exceeding control [mean 21.4 (18.5) nmol/L, p = 0.005]. Both sexes in the 25(OH)D group did not show significant increases in C-3 epimer, whereas 0.5 and 1 IU epimer groups exceeded 100 nmol/L of C-3 epimer by 8 weeks. These data suggest C-3 epimer is endogenously generated with higher intakes of VD. Endogenous and exogenous C-3 epimer accumulates in serum without impact upon bone health outcomes in a healthy young adult model over 8 weeks.

Short-arm centrifugation as a partially effective musculoskeletal countermeasure during 5-day head-down tilt bed rest--results from the BRAG1 study.

Human centrifugation, also called artificial gravity (AG), is proposed as a combined strategy against detrimental effects of microgravity in long-term space missions. This study scrutinized human short-arm centrifugation as countermeasure against musculoskeletal de-conditioning. Eleven healthy male subjects [mean age of 34 (SD 7) years] completed the cross-over trial, including three campaigns of -6° head-down tilt bed rest (HDT) for 5days, with preceding baseline data collection and recovery phases. Bed rest without AG was used as control condition (Ctrl), and AG with 1g at the center of mass applied once per day for 30min in one bout (AG1×30) and in 6 bouts of 5min (AG6×5, 3-min rest between bouts) as experimental conditions. End-points were muscle strength, vertical jump performance, and biomarkers of bone and protein metabolism. AG6×5 was better tolerated than AG1×30. Bone resorption markers CTX, NTX, and DPD all increased by approximately 25% toward the end of bed rest (P<0.001), and nitrogen balance decreased by approximately 3g/day (P<0.001), without any protection by AG (P>0.4). Decreases in vertical jump height by 2.1 (SE 0.6) cm after Ctrl bed rest was prevented by either of the AG protocols (P=0.039). The present study yielded succinct catabolic effects upon muscle and bone metabolism that were un-prevented by AG. The preservation of vertical jump performance by AG in this study is likely caused by central nervous rather than by peripheral musculoskeletal effects.