Bone Turnover In Type Research Articles

Role of immunological and biochemical markers in bone turnover in type I diabetic patients in Karbala province, Iraq

Introduction & Aim: Long-term diabetes mellitus (DM) is known to have a deleterious impact on bone health, resulting in change in bone mineral density, bone turnover, and bone quality, all of which increase the risk of fractures. The aim of. this study was to link immunological and pro-inflammatory cytokine (I.L-6, I.L-1, and TNF-alpha) markers in patients.with type 1 diabetes to Their connection to bones formation (sPINP) and bone resorption parameters (sCTX). Materials & Methods: This study included 80 patients suffering from T1DM in the age range of 20-45 years. The patients were assayed for their biochemical (Vitamin D and HbA1c), Immunological (IL-6, IL-1 and TNF-alpha) parameters, as well as bone formation and resorption markers. Results: HbA1c values were observed to be 7.5 in 85% of individuals, while vitamin D levels were 16 ng/mL. Correlation in patients with HbA1c 7.5. The results of a linear regression between I.L-6 and sCTX showed that there was an increase in sCTX for each unit of IL-6. Conclusion: In patients with HbA1c levels 7.5, there is an association between IL-6, TNFalpha, and the bone resorption. TNF-alpha and IL-6 have been linked to metabolic control loss.

Determinants of Low Bone Turnover in Type 2 Diabetes-the Role of PTH

Determinants of low bone turnover in type 2 diabetes (T2DM) are poorly understood. To investigate the relationship between markers of bone turnover, glycaemic control, disease duration and calciotropic hormones in T2DM we assessed baseline biochemical data from the DiabOS Study, a prospective multicenter observational cohort study. In a cross-sectional study-design data from 110 postmenopausal women and men aged 50–75 years diagnosed with T2DM for at least 3 years and 92 non-diabetic controls were evaluated. Biochemical markers of bone formation (N-terminal propeptide of type I procollagen [PINP]), bone-specific alkaline phosphatase [BAP]) and resorption (C-terminal cross-linking telopeptide of type I collagen [CTX]), measures of calcium homeostasis (intact parathormone [iPTH], 25-Hydroxyvitamin D, calcium, magnesium) and glycaemic control were assessed. After adjustment for age, gender and body mass index (BMI), patients with T2DM had lower serum levels of PINP (p < 0.001), CTX (p < 0.001), iPTH (p = 0.03) and magnesium (p < 0.001) compared to controls. Serum calcium, creatinine, 25-Hydroxyvitamin D and sclerostin did not differ between both groups. In multivariate linear regression analyses only serum iPTH remained an independent determinant of bone turnover markers in T2DM (PINP: p = 0.02; CTX: p < 0.001 and BAP: p < 0.01), whereas glycated haemoglobin (HbA1c), disease duration, age and BMI were not associated with bone turnover. In conclusion low bone turnover in T2DM is associated with low iPTH. The underlying mechanism remains to be elucidated.

Thyroid and bone turnover markers in type 2 diabetes: results from the METAL study.

ObjectiveWe aimed to evaluate whether thyroid hormones, autoimmune and thyroid homeostasis status were related to bone turnover in type 2 diabetes.MethodsThe data were obtained from a cross-sectional study, the METAL study. In this study, 4209 participants (2059 men and 2150 postmenopausal women) with type 2 diabetes were enrolled. Thyroid function, thyroid antibodies and three bone turnover markers (BTMs), including a large N-mid fragment of osteocalcin (N-MID osteocalcin), β-C-terminal cross-linked telopeptides of type I collagen (β-CTX) and procollagen type I N-terminal propeptide (P1NP), were measured. Thyroid homeostasis parameters, including the sum activity of step-up deiodinases (SPINA-GD), thyroid secretory capacity (SPINA-GT), Jostel’s TSH index (TSHI) and the thyrotroph thyroid hormone resistance index (TTSI), were calculated. The associations of thyroid parameters with BTMs were analyzed using linear regression.ResultsFree and total triiodothyronine were positively associated with N-MID osteocalcin and P1NP in both sexes and positively associated with β-CTX in postmenopausal women. Thyroid-stimulating hormone was negatively associated with β-CTX in postmenopausal women, and free thyroxine was negatively associated with N-MID osteocalcin and P1NP in men. SPINA-GD was positively associated with N-MID osteocalcin and P1NP in both sexes. There was a positive relationship of SPINA-GT with β-CTX, a negative relationship of TTSI with β-CTX, and a negative relationship of TSHI with β-CTX and P1NP in postmenopausal women.ConclusionsAmong men and postmenopausal women with type 2 diabetes, significant associations were observed between N-MID osteocalcin, β-CTX and P1NP with thyroid function and thyroid homeostasis. Further prospective studies are warranted to understand the causal relationship and underlying mechanism.

The Effects of Diabetic Polyneuropathy and Autonomic Neuropathy on Bone Turnover.

Background: The effect of diabetic polyneuropathy (DPN) and autonomic neuropathy (AN) on bone turnover in type 2 diabetes mellitus (DM) is uncertain due to the lack of data. In this study, we tried to determine the effect of DPN and AN on bone metabolism. Materials and Methods: The study included patients with type 2 DM (aged 18-80 years) and age-matched healthy individuals who presented to the Departments of Metabolism and Diabetes, Geriatrics, and General Internal Medicine, Cerrahpaşa Medical School, Istanbul University. The patients were examined to find out whether they had AN, and neuropathy scores were recorded by exploring peripheral neuropathy. Bone mineral density was measured by dual-energy X-ray (DXA). Demographic characteristics, the presence of microvascular complications, and biochemical data were obtained from patients' files. Serum cross-linked C-telopeptide (Ctx), osteocalcin, and bone-specific alkaline phosphatase (B-ALP) were analyzed. Results: The study comprised a total of 64 patients: 23 had type 2 DM and osteoporosis (OP) (duration of diabetes 10.1 ± 7 years; mean age 63 ± 9.1 years; female/male 18/5; Group 1), 41 had type 2 DM and non-OP (duration of diabetes 10.3 ± 7.6 years; mean age 58 ± 7.4 years; female/male 30/11; Group 2), and 26 healthy volunteers made up the control group (mean age 62 ± 11.9 years; female/male 14/12; Group 3). The bone turnover parameters were lower in type 2 DM individuals. The levels of osteocalcin (13.3 ± 5.2 ng/mL) and B-ALP (44.7 ± 10.9 IU/L) in patients with type 2 DM were lower than those of healthy subjects: osteocalcin (20.6 ± 10 ng/mL) and B-ALP (111 ± 31.4 IU/L; P = 0.001 and P = 0.000, respectively). Ctx levels (193.5 ± 49.3; 207.6 ± 40 ng/mL) were recorded to be similar (P = 0.2). AN was also noted as a risk factor for OP. For patients without AN, the likelihood of developing OP (odds ratio) was 0.7. The corresponding ratio for patients with AN was 9.3. Conclusions: Among the independent variables, the neuropathy score was determined to have an impact on bone turnover. AN was identified to be a significant risk factor for OP.

Vitamin D is associated with blood lead exposure through bone turnover in type 2 diabetes patients.

BackgroundBone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes.MethodsA total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms.ResultsIn both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P < 0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL.ConclusionThe association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.

The role of RANKL and FGF23 in Assessing Bone Turnover in Type 2 Diabetic Patients.

Type 2 diabetes is a chronic metabolic disease which affects bone. There is evidence in the literature about some serum markers that reflect the bone turnover metabolism, such as RANKL (Receptor Activator of Nuclear factor Kappa-b Ligand) and Fibroblast Growth Factor (FGF) 23. We aimed to investigate the correlations between RANKL and FGF23 and other diabetes-related factors possibly influencing early bone turnover changes. We conducted a cross-sectional analytical study on a group of 171 patients with type 2 diabetes, without Charcot's arthropathy or a history of amputations, in which a complete history and anthropometric, clinical, biochemical and dietary evaluation were performed. We evaluated the serum level of RANKL and FGF 23. RANKL was significantly lower in patients with macroangiopathy (0.42±0.15 pmol/L vs. 0.47±0.2 pmol/L, p=0.001). The level of FGF23 was lower in patients with neuropathy (0.37±0.36 pmol/L vs. 0.41±0.17 pmol/L, p=0.001). We found that FGF23 increased with age, but decreased with the duration of diabetes. We also found an inverse relationship between FGF23 levels and HbA1c, triglycerides, diastolic blood pressure, total proteins, albuminemia. RANKL was significantly lower in patients with macroangiopathy, and FGF 23 in patients with neuropathy. Therefore, more studies are needed to elucidate their role in early bone turnover changes.

Increased Bone Turnover in Type 2 Diabetes Patients Randomized to Bariatric Surgery Versus Medical Therapy at 5 Years

The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial. This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index [BMI], 36.5 ± 3.6 kg/m2) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% [78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed. Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB ( P<.001) and 61.1 ± 90% in SG ( P<.001) compared to 29.8 ± 93% in IMT ( P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB ( P<.001) and 71 ± 69% in SG ( P<.001) compared to 43.8 ± 121.1% in IMT ( P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients ( P<.001). Increase in CTX correlated with decreased BMI in SG patients ( P = .039). In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients. BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione.

Effects of low-intensity pulsed electromagnetic fields on bone microarchitecture, mechanical strength and bone turnover in type 2 diabetic db/db mice

Type 2 diabetic patients have impaired bone quality, leading to increased fracture risk. Substantial evidence demonstrates that pulsed electromagnetic fields (PEMF) could resist osteopenia/osteoporosis induced by estrogen deficiency and disuse. However, the effects of PEMF on osteopenia/osteoporosis associated with diabetes, especially for more prevalent type 2 diabetes, remain poorly understood. We herein investigated the skeletal effects and mechanisms of PEMF (15 Hz, 20 Gs) on leptin receptor-deficient db/db mice with typical type 2 diabetic symptoms. Our µCT results showed that 12-week PEMF exposure significantly improved both cancellous and cortical bone microarchitecture in db/db mice. Three-point bending and biomechanical indentation testing demonstrated that PEMF improved whole-bone structural properties and tissue-level material properties in db/db mice. PEMF significantly promoted bone formation in db/db mice evidenced by increased serum osteocalcin and bone mineral apposition rate, whereas PEMF exerted no observable alteration in bone resorption. Real-time PCR showed that PEMF upregulated tibial gene expression of osteoblastogenesis-related of canonical Wnt/β-catenin signaling but not osteoclastogenesis-related RANKL-RANK signaling in db/db mice. Our findings demonstrate that PEMF improved bone quantity and quality with obvious anabolic activities in db/db mice, and imply that PEMF might become a clinically applicable treatment modality for improving bone quality in type 2 diabetic patients.

Nanoindentation time-dependent deformation/recovery suggestive of methylglyoxal induced glycation in calcified nodules

Although empirical findings have indicated increase in bone fracture risk in type 2 diabetes patients, that has yet to be proven by results obtained at the material level. Here, we report evidence showing nanoscale time-dependent deformation/recovery of in vitro calcified nodules mimicking bone turnover in type 2 diabetes in respect to methylglyoxal (MG)-induced glycation. Nanoindentation test results revealed that calcified nodules cultured with MG did not show adequate dimensional recovery, despite a large creep rate during constant load indentation testing. This lesser recovery is likely based on the linear matrix polymerization network formed by advanced glycation end products (AGEs) as a secondary product of MG. Since elevated serum MG and abnormal bone turnover related to the amount of AGEs are observed in cases of type 2 diabetes, this time-dependent behavior may be one of the factors of the bone fracture mechanism at the material level in affected patients.

Markers of Bone Turnover and 25-Hydroxy Vitamin D in Women with Type 2 Diabetes and Newly Diagnosed Osteoporosis

Abstract Background and Aims: The aim of the present study was to evaluate the characteristics of bone turnover markers and 25-hydroxy vitamin D levels in women with type 2 diabetes and recently diagnosed postmenopausal osteoporosis. Material and Methods: We performed a retrospective study that included 80 women with newly diagnosed postmenopausal osteoporosis: 40 women with type 2 diabetes (diabetic group) and 40 women without diabetes (non-diabetic group). For data collection we used the patients database of the National Institute of Endocrinology ”C.I. Parhon”, Bucharest, Romania. Results: Women with type 2 diabetes had significantly reduced levels of osteocalcin and crosslaps than non-diabetic women. In the diabetic group, alkaline phosphatase and 25-hydroxy vitamin D were lower than in non-diabetic women but without statistical significance. There was not statistically significant difference of bone mineral density (BMD) between diabetic and non-diabetic groups. Magnesium was significantly lower in diabetic women compared with non-diabetic women. Conclusions: Our results demonstrated a low bone turnover in type 2 diabetic women and it was shown an insufficiency of 25-hydroxy vitamin D in both studied groups. These findings should be taken into account when screening these patients for diabetes complications.

Selected markers of bone turnover in type 2 diabetic patients

The mechanisms of bone alterations in diabetes mellitus type 2 (DM2) are complex and still poorly understood. It depends on the number of protective factors on bone health, such as hyperinsulinemia, obesity, estrogens as well as factors accelerating bone resorption (e.g. hyperglycemia). The aim of this study was to evaluate the concentrations of CTx (C-terminal cross-linked telopeptide of the alpha chain of type I collagen) and OCN (osteocalcin) in DM2 patients and to look for correlations between these markers and selected clinical data as well as biochemical parameters evaluated in routine diagnostics and monitoring of diabetes (glucose, lipid profile, urea, creatinine, parathyroid hormone, HbA1c, ALT, AST and alkaline phosphatase). The study was conducted in 45 patients with type 2 diabetes aged 60.7±10.3 years. The control group consisted of 25 healthy subjects aged 57.6±11.9 years. In DM2 patients the concentrations of OCN (14.5±8.8 ng/ml; p&lt;0.001), CTx (0.3±0.2 ng/ml; p&lt;0.05) were significantly lower than in healthy subjects (28.1±11.9 ng/ml, 0.5±0.2 ng/ml for OCN and CTx, respectively). Significantly higher levels of OCN (p&lt;0.05) and CTx (p&lt;0.01) were found in women than in men within the study group. In DM2 patients OCN concentration was positive correlated with CTx ​​(r=0.721, p=0.000), PTH (r=0.426, p=0.003) and negative with TG ​​(r=-0.349, p=0.019). Furthermore, CTx was directly correlated with ALP ​​(r=0.396, p=0.009) and PTH (r=0.413, p=0.005) as well as inversely with TG (r=-0.302, p=0.044) and HbA1c (r=-0.349, p=0.019). In conclusion, the observed lower levels of OCN and CTx and their positive inter-correlation may suggest overall slowed down bone metabolism with reduced bone formation and bone resorption in patients with DM2.

Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus

Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling. The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. This was a cross-sectional study. The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay. Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50-2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20-7.62, respectively; P=0.0002). β-Catenin correlated negatively with sclerostin (P<0.0001) and positively with bone alkaline phosphatase (P=0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.

Circulating Sclerostin Levels and Bone Turnover in Type 1 and Type 2 Diabetes

Previous observations showed a condition of low bone turnover and decreased osteoblast activity in both type 1 and 2 diabetes mellitus (DM1 and DM2). Sclerostin is a secreted Wnt antagonist produced by osteocytes that regulates osteoblast activity and thus bone turnover. Its levels increase with age and are regulated by PTH. The aim of the present study was to evaluate circulating sclerostin levels in patients with DM1 or DM2 with normal renal function and to analyze its relationship with PTH, 25-hydroxyvitamin D, and bone turnover markers. DESIGN, AND SETTING: This was a cross-sectional study conducted at a clinical research center. Forty DM2 and 43 DM1 patients were studied and compared with a reference control group (n = 83). In the overall cohort, sclerostin levels were higher in males than in females and significantly increased with age in both genders. The positive correlation between sclerostin and age was maintained in DM1 but not in DM2 patients. Moreover, sclerostin levels were higher in DM2 than in controls or DM1 patients, and this difference persisted when adjustments were made for age and body mass index. Consistent with previous clinical and experimental observations, sclerostin was negatively associated with PTH in nondiabetic patients (r = -0.30; P < 0.01), independently of age and gender. Conversely, an opposite but nonsignificant trend between PTH and sclerostin was observed in both DM1 (r = 0.26; P = 0.09) and DM2 (r = 0.32; P = 0.07) cohorts. These findings suggest that sclerostin is increased in DM2. Moreover, the transcriptional suppression of sclerostin production by PTH might be impaired in both DM1 and DM2.

Poor glycemic control is associated with low BMD detected in premenopausal women with type 1 diabetes

The etiology of bone fragility in individuals with type 1 diabetes is unknown. This study demonstrated that bone turnover favors resorption and that poor glycemic control is associated with low bone mineral density (BMD) and low bone turnover, in premenopausal women with type 1 diabetes. The results could inform future interventions. Low BMD and fracture may be complications of type 1 diabetes. We sought to determine the roles of bone turnover and glycemic control in the etiology of low BMD. Premenopausal women from the Wisconsin Diabetes Registry Study and matched controls were compared (n = 75 pairs). Heel and forearm BMD were measured, and hip and spine BMD were measured in a subset. Markers of bone formation (osteocalcin) and resorption (NTx), and glycemic control (HbA1c) were determined. Age ranged from 18 to 50 years with a mean of 28, and 97% were Non-Hispanic white. Among women with diabetes, mean disease duration was 16 years and current HbA1c was 8%. Compared to controls, women with diabetes had a high prevalence of previous fracture (37% vs. 24%) and low BMD for age (heel or forearm: 49% vs. 31%), low heel and forearm BMD, and low osteocalcin levels. Levels of NTx were similar, suggesting uncoupled turnover favoring resorption. Poor glycemic control was associated with low BMD at all bone sites except the spine, and with low osteocalcin and NTx levels. Optimal glycemic control may prevent low BMD and altered bone turnover in type 1 diabetes, and decrease fracture risk.

Zinc Intake and Biochemical Markers of Bone Turnover in Type 1 Diabetes

OBJECTIVE—To examine the relationship between Zn nutritive status and biochemical markers of bone turnover in type 1 diabetes.RESEARCH DESIGN AND METHODS—Serum osteocalcin, urine N-telopeptides, and dietary intake data, obtained by 3-day food records, were assessed for 66 individuals with type 1 diabetes.RESULTS—Zn intake correlated with osteocalcin in the group overall (r = 0.48; P < 0.001) but not with N-telopeptides. Examined by sex, both Zn and osteocalcin correlated for men (r = 0.57; P < 0.001), but the correlation did not reach statistical significance for women (r = 0.34; P = 0.09). A direct-entry linear regression model with osteocalcin as the dependent variable was performed. Duration, sex, A1C, insulin use per kilogram, total calorie intake, and Zn intake were entered as potential independent variables. The model was statistically significant (R2 = 0.32; P < 0.01). Zn intake (P < 0.001), however, was the only independent correlate of osteocalcin.CONCLUSIONS—This study provides evidence of a positive relationship between Zn intake and osteocalcin in type 1 diabetes.

Bone metabolism in male patients with type 2 diabetes

Few reports are available on bone turnover in type 2 diabetes. Impaired bone turnover in type 2 diabetes appears to result from decreased bone formation. Studies also suggest that poor glycaemic control in type 2 diabetes may contribute to osteopaenia. The aim of this study was to investigate biochemical markers of bone turnover in males with poorly controlled type 2 diabetes and look for correlations with glycaemic control and gonadal and hypophyseal hormonal axis. Consecutive male patients with poorly controlled type 2 diabetes and attending the internal medicine department during a period of 6 months were enrolled. The patients were receiving oral hypoglycaemic agents (metformin or sulphonylureas or both). None of the patients had any evidence of macroangiopathy, nephropathy or neuropathy. Only two patients had proliferative retinopathy. Serum osteocalcin, crosslaps (C-telopeptide, CTx), parathyroid hormone (PTH), testosterone, oestrogen, prolactin, follicle-stimulating hormone (FSH) and luteinising hormone (LH) were measured in 35 patients and 35 controls. The mean age of the study population was 53.7 (10.3) years (range: 50.2-57.3) and the mean disease duration was 8.6 (6.0) years (range: 6.5-10.7). No differences between patients and controls were observed in serum calcium, phosphorus, creatinine, albumin, PTH, CTx, oestrogen, testosterone, LH, FSH, prolactin and urinary calcium. Patients had lower serum levels of osteocalcin than controls with a significant statistical difference [15.3 (4.1) vs 18.3 (5.3), p=0.012]. There was a negative significant statistical correlation between CTx levels and HbA1c (r=-0.41, p< 0.05). Our study suggested that bone formation is altered in type 2 diabetes and that bone turnover is affected by glycaemic control status.

Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption.

The aims of the study were to evaluate the use of bone-specific biochemical markers of turnover in type I osteoporosis, to test for evidence of heterogeneity of bone turnover in this condition, and to attempt to devise an 'uncoupling index' by using the relationship between bone-specific biochemical markers of bone formation and bone resorption. In women with type I osteoporosis (mean age 64 years, SD 5; n = 63) the mean level of serum osteocalcin, a specific biochemical marker of bone formation, was 9.9 ng/ml (SD 2.0), which was higher than the level in normal postmenopausal women (mean age 65 years, SD 6; n = 8.9 ng/ml (SD 2.0; p < 0.01). The variance of serum osteocalcin levels in the two groups was similar. Compared with this 11% increase in the biochemical marker for bone formation, the markers of bone resorption, total urinary deoxypyridinoline (bone-specific), pyridinoline and hydroxyproline were increased by 40% (p < 0.0001), 61% (p < 0.0001) and 25% (p < 0.01), respectively. Furthermore, these biochemical markers of bone resorption had greater variance in women in type I osteoporosis than in the normal postmenopausal women (p < 0.01). The urinary excretion of the free crosslinks deoxypyridinoline, pyridinoline and glycosylated pyridinoline were increased by 26% (p < 0.001), 17% (p < 0.01) and 13% (NS) respectively. An 'uncoupling index' was calculated for the difference between urinary deoxypyridinoline and serum osteocalcin using the results from the normal women and expressed as z-scores. We conclude that the pyridinium crosslinks of collagen enable better discrimination between normal and osteoporotic women than does hydroxyproline.(ABSTRACT TRUNCATED AT 250 WORDS)