Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus

BackgroundEmerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D.MethodA cross-sectional analysis of baseline data was obtained from 217 men, ages 35–65, regardless of the presence or absence of hypogonadism or T2D, who participated in 2 clinical trials. The following data were obtained: A1c by HPLC, testosterone and estradiol by LC/MS, bone turnover markers Osteocalcin [OC], C-terminal telopeptide [CTx], and sclerostin by ELISA, and BMD by DXA. Patients were grouped into 4 categories based of A1c (group I: <6%, group II: 6.0–6.4%, group III: 6.5–6.9%, and group IV: ≥7%). Threshold models were fit to the data using nonlinear regression and group comparisons among the different A1c categories performed by ANOVA.ResultsThreshold model and nonlinear regression showed an A1c cut-off of 7.0, among all choices of A1cs, yields the least sum of squared errors. A comparison of bone turnover markers revealed relatively lower OC (p = 0.002) and CTx (p = 0.0002) in group IV (A1c ≥7%), compared to the other groups. An analysis of men with T2D (n = 94) showed relatively lower OC (p=0.001) and CTx (p=0.002) in those with A1c ≥7% compared to those with <7%, respectively. The significance between groups persisted even after adjusting for medications and duration of diabetes.ConclusionAn analysis across our entire study population showed a breakpoint A1c level of 7% or greater is associated with lower bone turnover. Also in men with T2D, an A1c ≥7% is associated with low bone turnover.

Prebiotic to Improve Calcium Absorption in Postmenopausal Women After Gastric Bypass: A Randomized Controlled Trial

Context The adverse skeletal effects of Roux-en-Y gastric bypass (RYGB) are partly caused by intestinal calcium absorption decline. Prebiotics, such as soluble corn fiber (SCF), augment colonic calcium absorption in healthy individuals. Objective We tested the effects of SCF on fractional calcium absorption (FCA), biochemical parameters, and the fecal microbiome in a post-RYGB population. Design, Setting, Participants : Randomized, double-blind, placebo-controlled trial of 20 postmenopausal women with history of RYGB mean 5 years prior. Intervention 2-month course of 20 g/day SCF or maltodextrin placebo orally. Main Outcomes Between-group difference in absolute change in FCA (primary outcome) was measured with a gold-standard dual stable isotope method. Other measures included tolerability, adherence, serum calciotropic hormones and bone turnover markers, and fecal microbial composition via 16S rRNA gene sequencing. Results Mean FCA ±SD at baseline was low at 5.5±5.1%. Comparing SCF to placebo, there was no between-group difference in mean (95% CI) change in FCA (+3.4 [-6.7,+13.6]%), nor in calciotropic hormones or bone turnover markers. The SCF group had a wider variation in FCA change than placebo (SD 13.4% vs. 7.0%). Those with greater change in microbial composition following SCF treatment had greater increase in FCA (r 2=0.72,p=0.05). SCF adherence was high, and GI symptoms similar between groups. Conclusions No between-group differences were observed in changes in FCA or calciotropic hormones, but wide confidence intervals suggest a variable impact of SCF that may be due to the degree of gut microbiome alteration. Daily SCF consumption was well-tolerated. Larger and longer-term studies are warranted.

Efficacy and Safety of Oral Ibandronate versus Intravenous Zoledronic Acid on Bone Metabolism and Bone Mineral Density in Postmenopausal Japanese Women with Osteoporosis

There are no published clinical reports comparing ibandronate (IBN) treatment and zoledronic acid (ZOL) treatment in Japanese postmenopausal osteoporotic patients. This investigation therefore compared the efficacy and safety of the drugs on improving bone metabolism and bone mineral density (BMD) in Japanese postmenopausal women with primary osteoporosis. Eighty-two treatment-naïve primary osteoporotic female patients were randomly divided into IBN-treated or ZOL-treated groups. Bone turnover markers and BMD were examined immediately prior to treatment (baseline) and at 6, 12, 18, 24, and 30 months of therapy. Compared with baseline levels, the values of type 1 procollagen N-terminal propeptide, bone-specific alkaline phosphatase (BAP), urinary type-I collagen amino-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b were all significantly decreased at every time point in both groups apart from BAP at 30 months in the ZOL group, urinary NTX at 12 months in the ZOL group and at 24 and 30 months in both groups. Lumbar BMD values were significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6 and 12 months in the ZOL group compared with pre-treatment levels. Hip BMD values were also significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6, 12, and 18 months in the ZOL group compared with baseline values. The percentage changes of hip BMD at 18 and 24 months in the ZOL group were significantly higher than those in the IBN group (both p < 0.05). No remarkable adverse events were noted in either group. In conclusion, both IBN and ZOL significantly and safely improved bone turnover markers and BMD during 30 months of treatment in Japanese osteoporosis patients. The ZOL group tended to exhibit greater gains in BMD as compared with the IBN group, which merits further investigation.

Association between biomarkers of bone health and osteosarcopenia among Iranian older people: The Bushehr Elderly Health (BEH) program

Background Osteosarcopenia is referred to as co-incidence of osteoporosis/osteopenia and sarcopenia which is defined as a geriatric syndrome with a significant prevalence that increases morbidity and mortality. There are some relevant factors that can show an increased risk of incidence of osteosarcopenia. Aim We aimed to consider the association of bone turnover markers such as Osteocalcin (OC), C-terminal cross-linked telopeptide (CTX), Tartrate Resistant acid Phosphatase (TRAP), Bone Alkaline Phosphatase (BALP) and also other factors like vitamin D, calcium, phosphorous, and ALP with osteosarcopenia in elderly. Methods We carried out a cross-sectional study on a random sample including 400 elder participants of Bushehr Elderly Health (BEH) study, in Iran. Osteopenia/ osteoporosis was defined as a T-score ≤ -1.0 standard deviation below the mean values of a young healthy adult. We defined sarcopenia as low muscle strength (handgrip strength<26 kg for men and <18 kg for women) with reduced skeletal muscle mass [Skeletal muscle index (SMI) < 7.0 kg/m2 for male and <5.4 kg/m2 for female]. Osteosarcopenia was considered as the presence of both osteopenia/osteoporosis and sarcopenia. We estimated the age-standardized prevalence of osteosarcopenia for men and women, separately. We used multivariable logistic regression to address the factors associated with osteosarcopenia. Results The results showed that there was a statistically significant difference in OC), CTX, TRAP were between the osteosarcopenia (-) and osteosarcopenia (+) groups. No statistically significant difference was observed in BALP, vitamin D, calcium, phosphorous, and ALP between the compared groups. In the multivariable logistic regression model, OC and CTX were associated with increased likelihood of osteosarcopenia [adjusted OR= 1.023(1.002-1.045 for OC, 4.363(1.389-15.474 for CTX)]. Furthermore, TRAP increases the odds of osteosarcopenia in crude model [OR= 1.333 (1.070- 1.660)]. Conclusions We observed the association between bone turnover markers particularly OC, CTX and osteosarcopenia. Given the rapid growth of the aging population, we should focus on geriatric diseases such as musculoskeletal disorders. Bone turnover markers maybe improve the early diagnosis, screening and assess the response to therapies in people with osteosarcopenia.

Clinical significance of Vitamin-D and other bone turnover markers on bone mineral density in patients with gestational diabetes mellitus

Objectives: To perform a correlation analysis of serum 25-hydroxy Vitamin-D[25-OH-D], bone turnover markers (BTMs), and bone mineral density (BMD) in patients with gestational diabetes mellitus (GDM) during mid- and late pregnancy and state the significance of these factors for guiding clinical prevention and control of GDM. Methods: This study involved 100 pregnant women with singleton pregnancies who visited our obstetrics and gynecology department, Baoding First Central Hospital, during January 2019 and December 2020. All participants had received more than five prenatal checkups and were assigned to a GDM group and a normal group according to the presence of GDM during the mid-pregnancy period. Serum 25-OH-D, BMD, and bone turnover markers (BTMs) were measured to analyze the differences between the two groups and observe possible correlations among these factors. Results: According to the examination results, GDM occurred in 31 (31%) participants, and the rest 69 (69%) were free of GDM during mid-pregnancy. No significant differences were observed between the two groups in basic clinical data and the serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (p>0.05), whereas the fasting blood glucose (FBG) level in the GDM group was significantly higher than in the normal group (p<0.05). The serum 25-OH-D and BMD levels in the GDM group were lower than in the normal group, whereas the bone alkaline phosphatase (BALP), osteocalcin (OC), procollagen type I propeptide (PINP), and beta-isomerized C-terminal telopeptide (β-CTx) levels in the GDM group were significantly higher than in the normal group, with the differences showing statistical significance (p<0.05, respectively). The results of Pearson’s correlation analysis revealed that serum 25-OH-D was positively correlated with BMD (r =0.183, P <0.05) and negatively correlated with such BTMs as BALP, OC, PINP, and β-CTx (r =-0.255, -0.369, -0.204, -0.610; p<0.05). Conclusion: During mid and late pregnancy, GDM patients are prone to Vitamin-D deficiency, which has an adverse effect on bone turnover, BMD, and even the health of the mother and the development of the fetus. Therefore, routine screening for Vitamin-D deficiency is recommended throughout pregnancy. doi: https://doi.org/10.12669/pjms.38.1.4461 How to cite this:Ma J, Han L, Zhou X, Li Z. Clinical significance of Vitamin-D and other bone turnover markers on bone mineral density in patients with gestational diabetes mellitus. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4461 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.