Although inflammation is known to influence bone turnover and bone mineral density (BMD), less is known about role of soluble tumor necrosis factor alpha receptor 1 (sTNFα-R1) in changes in bone turnover and BMD in the year after hip fracture. We studied 245 persons (117 men and 128 women) from the Baltimore Hip Studies. Bone turnover markers of resorption (carboxy-terminal type I collagen cross-links [CTX-I]) and formation (amino-terminal propeptide type I collagen [P1NP]), BMD of the contralateral hip, and sTNFα-R1 were measured within 15 days of hospitalization and 2, 6, and 12 months later. Latent class growth modeling was used to determine sTNFα-R1 trajectories. Weighted generalized estimating equations were used to examine the association of sTNFα-R1 trajectories with serum levels of CTX-I and P1NP and BMD; standardized beta coefficients (βˆ) are reported. Higher baseline sTNFα-R1 was significantly associated with a greater rate of CTX-I change (βˆ = 0.26, p = 0.004). Four distinct sTNFα-R1 trajectories were identified. The two groups with higher sTNFα-R1 levels during the year following fracture had faster increasing levels of CTX-I compared to the group with lowest sTNFα-R1 levels (men: group 3: βˆ = 0.76, p = 0.02; group 4: βˆ = 1.4, p < 0.001; women: group 3; βˆ = 0.67, p = 0.02; group 4: βˆ = 1.3, p = 0.004). Men in the highest sTNFα-R1 group had a greater decline in BMD compared to the lowest sTNFα-R1 group (2-month βˆ = -0.01, p = 0.01; 6-month: βˆ = -0.09, p = 0.001; 12-months: βˆ = -0.1, p < 0.001). An increasing rate of CTX-I was associated with a steeper decline in total hip BMD in those within higher sTNFα-R1 trajectory groups (p < 0.001). CTX-I was significantly increased with sTNFα-R1 in both sexes. CTX-I and the highest sTNFα-R1 trajectory were significantly associated with declines in total hip BMD in men. Interventions that reduce systemic inflammation should be explored to reduce bone resorption and prevent a decline in BMD after hip fracture. © 2018 American Society for Bone and Mineral Research.

Preserving a patient's own teeth-even in a difficult situation-is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20-23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-β1 (TGF-β1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.

BACKGROUND

Undercarboxylated osteocalcin (ucOC) modulates insulin secretion and sensitivity in mice, and higher ucOC is associated with lower prevalence of diabetes in men. The influence of ucOC distinct from other markers of bone turnover on incidence of cardiovascular events is unclear.

METHODS

Community-dwelling men aged 70-89 years resident in Perth, Western Australia.

METHODS

Serum total osteocalcin (TOC), N-terminal propeptide of type I collagen (P1NP), and collagen type I C-terminal cross-linked telopeptide (CTX) were measured by immunoassay, and ucOC by hydroxyapatite binding. The ratio ucOC/TOC was calculated. Hospital admissions and deaths from myocardial infarction (MI) and stroke were ascertained.

RESULTS

There were 3384 men followed for 7.0 years, during which 293 experienced an MI, 251 stroke, and 2840 neither. In multivariate analyses, higher ratio of ucOC/TOC (expressed as %) was associated with lower incidence of MI (quartiles Q2-4, ≥ 49% versus Q1,<49%, hazard ratio 0.70, 95% confidence interval = 0.54-0.91), but not of stroke (0.99, 0.73-1.34). Higher P1NP was associated with higher incidence of MI (Q2-4, ≥ 28.2 μg/L versus Q1, <28.2 μg/L, hazard ratio 1.45, 95% confidence interval = 1.06-1.97), but not of stroke (0.94, 0.70-1.26). CTX was not associated with incident MI or stroke.

CONCLUSIONS

A reduced proportion of undercarboxylated osteocalcin or higher P1NP are associated with increased incidence of MI. UcOC/TOC ratio and P1NP predict risk of MI but not stroke, in a manner distinct from CTX. Further studies are needed to investigate potential mechanisms by which bone turnover markers related to metabolic risk and to collagen formation could modulate cardiovascular risk.

Several studies suggest that neutralizing acid load in the diet with alkali had favorable effects on intermediate markers of musculoskeletal health. We examined whether alkali supplementation with potassium bicarbonate [(KHCO3); 81 mmol/d; n = 12] vs placebo (n = 12) for 84 days altered serum microRNAs, potential biomarkers associated with innumerable biological processes including bone and muscle metabolism. Serum microRNAs, urinary net acid excretion (UNAE), urinary N-telopeptide (UNTX), urinary calcium (UCa), urinary nitrogen (UN), glomerular filtration rate, serum procollagen type 1 amino-terminal propeptide (P1NP), serum insulin-like growth factor-1 (IGF-1), and its serum binding protein IGFBP3 were measured at baseline and day 84. Baseline characteristics and measurements were similar in the two treatment groups. Eighty-four-day changes in UNAE differed by group (KHCO3, -47 ± 9 mmol; placebo, -5 ± 5 mmol; P < 0.01). KHCO3 significantly reduced UNTX, UCa, and serum P1NP but did not affect UN, serum IGF-1, or IGFBP3 levels compared with placebo over 84 days. Fold change in serum circulating microRNA (c-miR)-133b differed significantly by group (KHCO3, 2.26 ± 0.85; placebo, -1.23 ± 0.69; P < 0.01); there was a similar trend in c-miR-21-5p. Fold changes in c-miR-133b and c-miR-21-5p were inversely associated with changes in UNAE and UNTX; fold change in c-miR-21-5p was inversely associated with change in UCa, with a similar trend with c-miR-133b. In summary, reducing renal acid load with KHCO3 was associated with increased expressions of c-miR-133b and c-miR-21-5p. Furthermore, increases in c-miRNA-133b and c-miR-21-5p were inversely associated with bone resorption markers UNTX and UCa consistent with potential beneficial effects on bone in older adults. However, the broader significance of c-miRNAs as musculoskeletal biomarkers is still under investigation, and larger studies are needed to verify these preliminary results.

Calcium intake was negatively associated with bone resorption marker such as DPD, NTX, and P1NP in Japanese postmenopausal osteoporotic patients. Not only to suppress bone resorption but also to keep higher hip bone mineral density were observed in the patients with higher intake of calcium than 800mg/day and higher vitamin D condition (more than 50nmol/L of serum 25 (OH) D). Higher calcium intake than 800mg/day from dairy and Tofu products, higher intake of vitamin D than 10μg/day from fish, and higher intake of vitamin K from vegetables should be recommended in Japanese postmenopausal osteoporotic patients. We should also pay attention to their losing weight and excess intake of these nutrients from supplements.

OBJECTIVE

To determine the window of time during which osteoporosis affects the management of spinal surgery and the mechanism of bone metabolism changes in males with osteoporosis by examining changes in bone metabolism in young castrated male rats.

METHODS

A total of 30 Sprague-Dawley rats were randomly allocated into two study groups. Group 1 (control) received a sham surgery and Group 2 received bilateral orchiectomy to change bone mineral density (BMD). Serum osteocalcin, alkaline phosphatase (ALP), and collagen type 1 cross-linked C-telopeptide (CTX) were analyzed at postoperative date (POD) 8, 10, and 12 weeks. BMDs were measured using micro computed tomography scans.

RESULTS

Femoral and lumbar BMDs were decreased in the orchiectomy groups. BMDs in the sham and orchiectomy groups showed statistically differences at POD 8, 10, and 12 weeks for the femur (p=0.032, 0.008, 0.008) and lumbar spine (p=0.151, 0.008, 0.008, respectively). Serum osteocalcin, ALP, and CTX decreased gradually; however, N-terminal type 1 procollagen (P1NP) showed a slight increase yet no significant change.

CONCLUSIONS

In young castrated male rats, a significant decrease in BMD was observed after orchiectomy due to the mixture of two detrimental factors. Young castrated male rats did not reach peak BMD. Increased bone turnover causes bone resorption to exceed bone formation. This study may contribute to the creation of a valuable model for studies of male osteoporosis and the spinal surgery field.

BACKGROUND

Bone loss in celiac disease (CD) is important and is associated to increased risk of fractures. The determining factors of this Bone loss and the osteoporosis fracture during this disease remain still unknown. The bone remodeling parameters seem to play it an important role.

OBJECTIVE

Through a transverse study including 30 patients with adult CD and 30 witnesses, we estimated bone mineral density (BMD) profile of these patients and determined associated factors to the bone loss.

METHODS

Patients and witnesses benefited from an BMD measure, serum calcium and phosphore, alkaline phosphatasis, parathormone and hydroxyvitamin D dosage, bone remodeling parameters containing the osteocalcin, Propeptide N-terminal of the type I procollagen, BTélopeptide C-terminal ( B-CTX) of the type I procollagen I (bloody and urine CrossLaps). The patients benefited from a malabsorption bilan, a radiological examination of spine and an evaluation of the adhesion to the regime without gluten with a histological control.

RESULTS

Our population consists of 3 men (10 %) and 27 women (90 %) with an average age of 30.4 years (19-50 years). The average delay of the diagnosis of the MC is of 46.7 months. The alkaline phosphatases, the P1NP and the bloody crossLaps were more raised at the patient's with regard to the witnesses with respectively p=0.038, p=0.041 and p=0.021. The parathormone was also more raised at the patients but without significant difference 67.8 vs 53.8 ng / l. The DMO is low at 21 patients (70 %) versus 2 witnesses only (6.6 %), with an osteoporosis in 3 patients (10 %) and an osteopenia in 18 patients (60 %). Factors associated to the BMD decline are low body mass index, nulliparity, diagnostic delay>> to 2 years, the malabsorption syndrome, exaggerated intraepithelial lymphocytosis at the time of the histological control, an increase of bone remodeling parameters notably the alkaline phosphatasis, osteocalcin and bloody CrossLaps. While the BMD is more raised at the patient's having followed gluten regimens during more than 5 years. The age, the sex, the symptomatic character or not of the disease, the parathormone, hydroyviamin D and fractures are not correlated to the BMD profile patients.

CONCLUSIONS

The bone loss is more frequent during the adult CD than in the general population. His research has to become integrated into the coverage of this disease notably in the presence of risk factors. The absence of correlation between BMD loss and fractures underlines the importance of others factors in determining of bone fragility during this affection.

OBJECTIVE

To examine whether premenopausal women with distal radius fractures (DRF) have lower levels of 25-hydroxyvitamin D (25[OH]D) and increased levels of serum bone turnover markers (BTM) compared with control subjects without fracture.

METHODS

Premenopausal women with DRF (n = 20) were prospectively enrolled and compared with age-matched individuals without a fracture (n = 20). Outcome measures included serum levels of 25(OH)D, parathyroid hormone (PTH), markers of bone formation (osteocalcin [OC], N-terminal extension propeptide of type I collagen [P1NP], and bone-specific alkaline phosphatase [BSAP]), and markers of bone resorption (C-terminal telopeptide of type I collagen [CTX]). We assessed associations between BTM and DRF with conditional logistic regression and the utility of markers for fracture prediction with a receiver operator characteristic analysis.

RESULTS

The fracture group and control group were comparable in terms of age at menarche and BMI. Patients who had fractures had significantly greater levels of OC and P1NP, and demonstrated a nonsignificant increase in CTX. Levels of 25(OH)D, PTH, and BSAP were similar between groups. Conditional logistic regression revealed independent associations between DRF and increased levels of OC and CTX. Levels of 25(OH)D and PTH were not associated with DRF. Receiver operator characteristic analyses demonstrated moderate performance for OC, P1NP, BSAP, and CTX in predicting DRF.

CONCLUSIONS

Levels of 25(OH)D were not associated with DRF in premenopausal women. However, patients with DRF had increased levels of BTM of formation and resorption. Bone turnover markers may be helpful in predicting future fragility fractures in premenopausal women.

METHODS

Prognostic II.

BACKGROUND

Combination antiretroviral therapy (cART) may affect vitamin D [25(OH)D], parathyroid hormone (PTH), bone mineral density (BMD) and bone turnover (BT). Reduced BMD and secondary hyperparathyroidism have been reported with tenofovir (TDF). We investigated the associations between TDF and bone markers, especially in 25(OH)D-deficient patients.

METHODS

In a single-centre longitudinal study investigating BMD in HIV-positive men, serum 25(OH)D, calcium, phosphate, PTH and alkaline phosphatase (ALP) were measured. Lumbar spine, non-dominant total hip and non-dominant femoral neck BMD (g/cm(2)) were measured using dual-energy X-ray absorptiometry. BT was assessed by serum type 1 procollagen (P1NP) and carboxy-terminal collagen cross-links (CTX). Mann-Whitney U tests compared serum markers and BT, and t-tests compared BMD according to TDF in all and 25(OH)D-deficient patients.

RESULTS

A total of 422 men were recruited: mean age 47 (SD 9.8) years, 94% white ethnicity, 93% MSM, diagnosed HIV positive for median 9.6 (IQR 5.0,15.5) years, median CD4 547 (IQR 411,696) cells/µL, HIV RNA <40 copies/mL in 87% (96% of those on cART). 25(OH)D (nmol/L) was normal (>75), insufficient (50-75), deficient (25-50) and severely deficient (<25) in 14%, 29%, 50% and 7%, respectively. Of 381 men on cART, 77% were currently on TDF. TDF was not associated with median calcium (p=0.69) or phosphate (p=0.52), but patients had higher (but normal) median ALP [81 (IQR 69,103) vs. 73 (IQR 60,89) IU/L, p=0.005) compared to non-TDF cART. There was no difference in the association between vitamin D and PTH according to whether someone currently was (r=0.11, p=0.06, Figure 1) or was not using TDF (r=0.12, p=0.29, Figure 1). TDF was also not associated with PTH, BMD or BT in either all patients on cART (Table 1a) or in patients with 25(OH)D deficiency (Table 1b).

CONCLUSIONS

In this largely TDF-experienced cohort of HIV-positive men, there was no association between TDF and 25(OH)D deficiency, hyperparathyroidism, reduced BMD or increased BT, although patients on TDF had higher but normal ALP. We found no evidence to support additional monitoring of bone markers in patients on TDF regardless of 25(OH)D status.

OBJECTIVE

To study relationships between serum ferritin and bone metabolism in patients with hip fragility fractures.

METHODS

This cross-sectional study included 76 postmenopausal women with hip fracture from Feburary 2011 to June 2012. The mean age of the women was (73 ± 10) years (range, 55-93 years) and the mean duration of menstruation was (22 ± 10)years (range, 5-50 years). Serum concentrations of ferritin, transferrin, alkaline phosphatase (ALP), amino-terminal extension peptide of type I collagen (P1NP), C-terminal telopeptides of type I collagen (β-CTX)and femoral and lumbar bone mineral density by dual-energy X-ray absorptiometry were measured. Bone metabolism was compared between normal and elevated ferritin groups with t-test, Pearson linear, partial correlation and multiple regression analysis examined associations between iron- and bone-related markers.

RESULTS

Serum ferritin concentration raised to (230 ± 146)µg/L, transferrin concentration reduced to (1.89 ± 0.33)g/L. P1NP concentration raised to (61 ± 32) ng/L when the concentration of serum ALP and β-CTX were in the normal range. T-scores for bone mineral density in the femoral neck (-2.0 ± 1.1) and lumbar (-2.1 ± 1.2) were below the normal ranges(-1.0-1.0). The subjects were divided into two groups according to serum ferritin concentration, normal group(serum ferritin concentration ≤ 150 µg/L, n = 25) and elevated group(serum ferritin concentration>> 150 µg/L, n = 51). Patients of elevated group had lower bone mineral density in femoral neck and lumbar than normal group(t = 3.13,2.89, P < 0.01), and higher P1NP, β-CTX concentration (t = -2.38, -3.59, P < 0.05) . In partial correlation analysis adjusted for confounders, serum ferritin concentration was correlated negatively with bone mineral density in both femoral neck and lumbar (r = -0.335,-0.295, P < 0.05), and positively with P1NP and β-CTX (r = 0.467,0.414, P < 0.05), but not correlated with ALP (r = 0.188, P>> 0.05). Transferrin concentration tended to be correlated positively with bone mineral density in both femoral neck and lumbar (r = 0.444, 0.262, P < 0.05) and negatively with ALP, P1NP and β-CTX(r = -0.326,-0.285,-0.278, P < 0.05).

CONCLUSIONS

Iron overload has a high prevalence in postmenopausal women with fragility fracture. Increased iron stores, which might lead to bone loss and lower bone mineral density by enhancing the activity of bone turnover, could be an independent factor to take effects on bone metabolism on postmenopausal women.

The objective of this study was to investigate the effect of hyperprolactinemia and high levels of insulin-like growth factor-I (IGF-I) on bone resorption and their relation with receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in patients with prolactinoma and acromegaly. Thirty-one patients with acromegaly, 28 patients with prolactinoma, and 33 healthy individuals were included in the study. Serum concentrations of RANKL, OPG, bone alkaline phosphatase (bone ALP), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and urine deoxypyridinoline (DPD) levels were detected and bone mineral density (BMD) was measured. Groups were not statistically different from each other with regard to serum levels of RANKL and OPG. The RANKL/OPG ratio was higher in the prolactinoma group than in the control group (p=0.046). A positive correlation between OPG and increasing age was detected in both the prolactinoma and control groups (r=0.524, p=0.004 and r=0.380, p=0.029, respectively). An inverse correlation was observed between IGF-I and OPG after excluding age in the prolactinoma group (r=-0.412, p=0.046). OC and bone ALP were negatively associated with RANKL in the acromegaly group (r=-0.384, p=0.036 and r=-0.528, p=0.003, respectively). There was an inverse correlation between OPG and BMD at the femoral neck in the acromegaly group (r=-0.422, p=0.02). The effect of IGF-I on bone remodeling may be partly mediated by RANKL and OPG. The RANKL/OPG ratio plays an important role in prolactinoma. A positive correlation of OPG with age and an inverse correlation with IGF-I favor the compensatory response of OPG against bone loss in the aging skeleton.

While changes in biochemical markers of bone turnover (BTM) have been reported to predict changes in bone mineral density (BMD), the relationship between changes in BMD and BTMs with combined antiresorptive/anabolic therapy is unknown.

In the DATA study, 94 postmenopausal osteoporotic women (ages 51-91) received either teriparatide 20-mcg SC daily, denosumab 60-mg SC every 6months, or both for 2years. Pearson's correlation coefficients (R) were calculated to determine the relationship between baseline and early changes in BTMs (as well as serum sclerostin) and 2-year changes in BMD.

In women receiving teriparatide, baseline BTMs did not correlate with 2-year BMD changes though 12-month increases in osteocalcin and P1NP were associated with 2-year increases in spine BMD. In women receiving denosumab, spine and hip BMD gains correlated with both baseline and changes in P1NP and C-telopeptide. In women receiving combined teriparatide/denosumab, while both baseline and decreases in P1NP were associated with spine BMD gains, distal radius increases were associated with less CTX suppression. Neither baseline nor changes in serum sclerostin correlated with BMD in any treatment group.

In women treated with teriparatide or denosumab, early BTM changes (increases and decreases, respectively) predict 2-year BMD gains, especially at the spine. In women treated with combined teriparatide/denosumab therapy, BMD increases at the distal radius were associated with less suppression of bone turnover. These results suggest that efficacy of combination therapy at cortical sites such as the radius may depend on residual bone remodeling despite RANKL inhibition.

We aimed at comparing markers of bone metabolism during unloading in young and older men, and to assess countermeasure effectiveness.

16 older (60±2 years) and 8 younger men (23±3 years) underwent bed rest (BR) for 14 days. A subgroup of the Older performed cognitive training during BR and supplemented protein and potassium bicarbonate afterwards. Biochemical markers of bone and calcium/phosphate metabolism were assessed.

At baseline urinary NTX and CTX were greater in younger than in older subjects (P<0.001), but increased during BR (P<0.001) by a similar amount (P>0.17). P1NP was greater in young than in older subjects (P<0.001) and decreased during BR in the Young (P<0.001). Sclerostin increased during BR across groups (P=0.016). No systematic effects of the countermeasure were observed.

In men, older age did not affect control of bone metabolism, but bone turnover was reduced. During BR formation markers were reduced only in younger men whereas resorption markers increased to a comparable extent. Thus, we assume that older men are not at an elevated, and possibly even at a reduced risk to lose bone when immobilized.

OBJECTIVE

Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has also been associated with fracture. It remains unclear whether variation in thyroid hormones within the euthyroid range modulates bone health, particularly among older men. We assessed whether thyroid stimulating hormone (TSH) and free thyroxine (FT4) are associated with bone turnover markers (BTMs) and predict hip fracture risk in community-dwelling older men without known thyroid disease.

METHODS

Prospective cohort study.

METHODS

Four thousand two hundred forty-eight men aged 70-89 years.

METHODS

Baseline blood samples were assayed for TSH, FT4, total osteocalcin (TOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX). Incidence of hip fracture events was ascertained to 2012. Associations of TSH and FT4 with BTMs were analysed at baseline using Pearson correlation coefficients, and with incident hip fracture using Cox proportional hazards regression.

RESULTS

After excluding men with pre-existing thyroid or bone disease, there were 3, 338 men for analysis. Of these, 3, 117 were euthyroid, 135 had subclinical hypothyroidism, and 86 had subclinical hyperthyroidism. Men with subclinical thyroid disease were older, and those with subclinical hyperthyroidism had lower creatinine than the other groups. After multivariate analysis, there were no associations found between FT4, TSH or subclinical thyroid dysfunction and BTMs at baseline. Neither subclinical thyroid dysfunction, TSH nor FT4 were predictive of incident hip fracture in our study population.

CONCLUSIONS

In euthyroid older men, TSH and FT4 were not associated with BTMs or incident hip fracture. Our findings differ from those previously described in postmenopausal women.

Myeloma bone disease (MBD) is a major cause of morbidity in multiple myeloma (MM). We investigated bone turnover markers (BTM) as relapse predictors and biomarkers for monitoring MBD. We measured C-terminal telopeptide of type I collagen (CTX-1), and Procollagen type 1 N Propeptide (P1NP) in 86 MM patients and 26 controls. CTX-1 was higher in newly diagnosed patients compared to control, remission and relapse (P < 0·05), and decreased following treatment. In the setting of relapse, a CTX-1 rise greater than the calculated least significant change (LSC) was observed in 26% of patients 3-6 months prior to relapse (P = 0·007), and in 60·8% up to 3 months before relapse (P = 0·015). Statistically significant changes in CTX-1 levels were also observed in patients who were with and without bisphosphonate therapy at the time of relapse. In patients with normal renal function, mean CTX-1 level was highest in the newly diagnosed group (0·771 ± 0·400 μg/l), and lowest in the remission group (0·099 ± 0·070 μg/l) (P < 0·0001). P1NP levels were not statistically different across the patient groups. We conclude that CTX-1, measured on an automated hospital laboratory platform, has a role in routine treatment monitoring and predicting relapse of MBD, even in patients on bisphosphonates.

Osteoporosis prevention is an important public health goal. Bone turnover markers are clinically measured to assess bone strength. C-terminal telopeptide of type I collagen (CTX) is released when collagens degrade and serves as an indicator of bone resorption. Simple CTX immunoassays are now available. However, serum CTX (sCTX) reference ranges for Japanese women are lacking. Procollagen type I N-propeptide (intact P1NP) reflects osteoblast activity, serving as a marker of bone formation. Because sCTX and intact P1NP are clinically applied as bone turnover markers, we determined reference ranges for both sCTX and intact P1NP in healthy Japanese women. We collected 228 blood samples from healthy Japanese women aged 19-83 years, grouped by age and menopausal status. We measured sCTX and intact P1NP and examined their correlation. sCTX values differed significantly between the two consecutive decade groups encompassing 19-39 years of age, intact P1NP values between 20 and 30 s, between post-menopausal 50 and 60 s, and between pre-and post-menopausal women in their 50 s. The mean sCTX of 91 healthy pre-menopausal women was 0.255 (0.100-0.653) ng/mL, the intact P1NP in 90 women 33.2 (17.1-64.7) μg/L. Corresponding values for post-menopausal women were 0.345 (0.115-1.030) ng/mL and 41.6 (21.9-79.1) μg/L. sCTX correlated with intact P1NP. Bone resorption markers are measured to assess anti-resorption agents, bone formation markers to assess the effects of bone-forming agents. The sCTX and intact P1NP reference values determined herein, in healthy Japanese women, are expected to be useful for osteoporosis treatment, assessment of fracture risk, and other clinical applications.

Studies suggest that optimal vitamin D status is required for the maximal effect of antiresorptive agents. We investigated the relationship between vitamin D status, serum parathyroid hormone (PTH) concentrations, and change in bone mineral density (BMD) following iv zoledronate and denosumab. We carried out a retrospective analysis of 111 patients, mean age 70 (SD 13) years, 89 women and 22 men, prescribed zoledronate and 43 postmenopausal women treated with denosumab for osteoporosis. We measured BMD at the lumbar spine (LS) and total hip (TH), serum 25 (OH) vitamin D, PTH, and bone turnover markers (plasma CTX, P1NP) at 1 year. In patients on zoledronate, BMD increased at the LS and TH (mean LS change [SEM] = 2.6 % [0.5 %], mean TH change = 1.05 % [0.5 %], p < 0.05). A significant increase in BMD was seen at the LS only in the denosumab group (p = 0.001). Significant decreases in CTX and P1NP were observed at 12 months in both treatment groups. At baseline and at 12 months, 34 % and 23 % of the patients on zoledronate had a serum vitamin D of <50 nmol/L, respectively. The mean PTH concentration in patients with 25 (OH) vitamin D <50 nmol/L was 44 ng/L (SEM 16.6). Patients with PTH concentration <44 ng/L had significantly higher increases in TH BMD compared to those with PTH >44 ng/L (zoledronate 1.9 [0.83] vs. -0.43 [0.81], p = 0.04; denosumab 4.1 [0.054] vs. -1.7 [0.04], p = 0.004). Optimal vitamin D status and PTH concentrations improve the skeletal response to zoledronate and denosumab.

Teriparatide(recombinant human PTH1-34, 20 μg daily subcutaneous injection)has been approved for osteoporosis patients at high risk of fracture in many countries including Japan. Teriparatide daily injection therapy has been reported to increase BMD, improve microarchitecture of bone, and reduce the risk of new vertebral fractures and that of non-vertebral fractures. Pharmakokinetic(PK)study after a single Teriparatide injection of the daily dose in healthy Japanese postmenopausal women(n=18)revealed very rapid achievement of peak blood level(median of tmax=0.25 hr)followed by fast disappearance from the blood(mean t1/2=0.708 hr, n=17). Consistent with these PK characteristics, a rapid increase in bone formation marker and later increase in bone resorption marker has previously been observed, which was described as a bone anabolic window. More recently, once weekly subcutaneous injection of teriparatide acetate(56.5 μg)has been reported to reduce the risk of new vertebral fractures compared with placebo and has been approved in Japan. PK study after injection of the higher weekly dose in healthy Japanese postmenopausal women(n=10)revealed a relatively slow achievement of the peak blood level(mean tmax=0.875 hr)compared to daily injections, followed by relatively slow disappearance from the blood(mean t1/2=1.295 hr). Consistent with these PK characteristics, an initial(<24 hr)transient decrease of bone formation markers(serum osteocalcin and P1NP)and transient increase of bone resorption markers(serum NTX and urinary CTX)were observed. However, afterword, the bone formation and resorption markers were increased and decreased, respectively, for longer than 1 week from the baseline levels. The relationship of pharmacokinetics, changes of bone turnover markers and BMD/fractures efficacy during daily versus weekly teriparatide treatment needs to be clarified.

Teriparatide (recombinant human PTH1-34 daily subcutaneous injection) has been approved for osteoporosis at high risk of fracture in many countries including Japan. Teriparatide daily injection therapy has been reported to increase BMD, improve microarchitecture of bone, and reduce the risk of new vertebral fractures and that of non-vertebral fractures. The observed rapid increase in bone formation marker and later increase in bone resorption marker has been described as a bone anabolic window. The accumulated information using data from global clinical trials further tested in the Phase 3 trial of Japanese patients suggests that P1NP monitoring may be a useful aid in the management of patients with osteoporosis during teriparatide daily injection treatment. Recently once weekly subcutaneous injection of teriparatide has been approved in Japan. Weekly teriparatide injection treatment has been reported to reduce the risk of new vertebral fractures compared with placebo. Regarding bone turnover markers, serum osteocalcin increased and urinary NTX decreased during the weekly teriparatide treatment.

UNASSIGNED

To examine the effects of daily weighted vest use during a dietary weight loss intervention, on (a) hip and spine bone mineral density (aBMD), and (b) biomarkers of bone turnover, in older adults with obesity.

UNASSIGNED

37 older (70.1 ± 3.0 years) adults with obesity (BMI=35.3 ± 2.9) underwent a 22 week dietary weight loss intervention (1100-1300 kcal/day) with (Diet+Vest; n=20) or without (Diet; n=17) weighted vest use (goal: 10+ h/day; weight added incrementally based on amount of weight lost). Total body weight; DXA-acquired aBMD of the total hip, femoral neck and lumbar spine; and biomarkers of bone turnover (OC, BALP, P1NP, CTX) were measured at baseline and follow up. General linear models, adjusted for baseline values of the outcome and gender, were used to examine intervention effects.

UNASSIGNED

Average weight loss was significant in both groups (-11.2 ± 4.4 kg and -11.0 ± 6.3 kg, Diet+Vest and Diet groups, respectively), with no difference between groups (p=0.91). Average weighted vest use was 6.7 ± 2.2 h/day. No significant changes in aBMD or biomarkers were observed, although trends were noted for total hip aBMD and BALP. Loss in total hip aBMD was greater in the Diet group compared with Diet+Vest (Δ: -18.7 [29.3, -8.1] mg/cm2 versus -6.1 [-15.7, 3.5] mg/cm2; p=0.08). BALP increased in the Diet+Vest group by 3.8% (Δ: 0.59 [-0.33, 1.50] μg/L) and decreased by -4.6% in the Diet group (Δ: -0.70 [-1.70, 0.31] μg/L, p=0.07).

UNASSIGNED

Weighted vest use during weight loss may attenuate loss of hip aBMD and increase bone formation in older adults with obesity. Further study is warranted.