Bone Metabolism In Patients Research Articles

A prospective randomized controlled trial of bone metabolism in patients with charcot foot

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcot’s foot) - is a progressive destructive inflammatory disease of the osteoarticular apparatus of the foot, untimely and inadequate treatment of which can lead to the formation of gross deformities. More often, DNOAP is unilateral, bilateral lesion is relatively rare. It is not always possible to trace the relationship between the debut of DNOAP with trauma and chronic hyperglycemia. There is data demonstrating the role of individual pro-inflammatory factors in the pathogenesis of DNOAP, however, studies combining the evaluation of various metabolic markers of Charcot’s foot formation are currently extremely poor. AIM: To evaluate the hormonal and metabolic markers of bone formation and resorption in patients with DNOAP and without this diabetic complication. METHODS: A prospective, controlled trial included 70 patients with type 2 diabetes mellitus (37 men and 43 women) who formed 2 groups: group 1 included patients with DNOAP, group 2 was formed by patients with diabetes without foot skeleton damage. All patients underwent a study of 1,25-OH-vitamin D, sclerostin, pro-MMP-1, C-terminal propeptide type 1 collagen (PICP), type 1 collagen, osteocalcin, PTH, 25-OH-vitamin D, beta-cross-slaps. RESULTS: The results of the studies confirmed the presence of vitamin D deficiency in all patients with diabetes mellitus included in the study, revealed the absence of statistically significant differences between the groups in the values of sclerostin, pro-MMP-1; 25-OH-vitamin D, type I collagen, and osteocalcin (p > 0.05). However, significant differences were found in the 1.25-OH vitamin D levels: patients with DNOAP presented the lower rates of 1,25-OH-vitamin D in comparison to control group (p <0.05). Beta-cross and PICP levels were significantly higher in DNOAP patients as well (p <0.05). Those findings show the more severe collagen degradation in patients with DNOAP and can be the genetically predisposed cause of DNOAP development. Though further studies are needed. CONCLUSION: In patients with DNOAP a decrease in 1,25-OH-vitamin D levels was found, as well as the alteration of the synthesis and destruction of collagen (beta-cross-slaps and PICP) compared to patients with diabetes mellitus without osteoarticular disorders.

The Impact of Mild Autonomous Cortisol Secretion on Bone Turnover Markers.

Several studies have reported increased risk of fragility fractures in patients with mild autonomous cortisol secretion (MACS), discordant to the degree of bone density deterioration. To evaluate the effect of MACS on bone metabolism in patients with adrenal adenomas. Cross-sectional study with prospective enrollment, 2014-2019. Referral center. 213 patients with adrenal adenomas: 22 Cushing syndrome (CS), 92 MACS and 99 nonfunctioning adrenal tumors (NFAT). Osteocalcin, procollagen I intact N-terminal (PINP), C-terminal telopeptide (CTX), sclerostin. Patients with CS demonstrated lower markers of bone formation compared with patients with MACS and NFAT (CS vs MACS vs NFAT: mean osteocalcin 14.8 vs 20.1 vs 21.3 ng/mL [P < 0.0001]; mean PINP 34.8 vs 48.7 vs 48.5 µg/L [P = 0.003]). Severity of cortisol excess was inversely associated with sclerostin (CS vs MACS vs NFAT: mean sclerostin 419 vs 538 vs 624 ng/L, [P < 0.0001]). In a multivariable model of age, sex, body mass index, cortisol, and bone turnover markers, sclerostin was a significant predictor of low bone mass in patients with MACS (OR 0.63 [CI 95%, 0.40-0.98] for each 100 ng/L of sclerostin increase).After adrenalectomy, osteocalcin, CTX, and sclerostin increased by a mean difference of 6.3 ng/mL, 0.12 ng/mL, and 171 pg/mL (P = 0.02 for all), respectively. Lower sclerostin level in patients with MACS reflects a reduction in osteocyte function or number associated with exposure to chronic cortisol excess. Increase in bone turnover markers after adrenalectomy suggests restoration of favorable bone metabolism.

Identification of metastasis in the skeleton bones in patients with breast and prostate cancer: markers of bone metabolism and MRI diagnostics

The purpose of the investigation is to study biochemical markers of bone metabolism in patients with breast cancer and prostate cancer during periods of stable remission and recurrence/metastasis and to assess their informative value in the diagnosis and monitoring of skeletal lesions. The study included 21 female patients with breast cancer and 18 male patients with prostate cancer. The start of monitoring is at least 3 years after complete tumor regression as a result of treatment: breast cancer – radical mastectomy, prostate cancer – radical prostatectomy. Markers of bone resorption (urine deoxypyridinoline, C-terminal telopeptide and tartrate-resistant acid phosphatase of blood serum) and osteogenesis (bone alkaline phosphatase and osteocalcin of blood serum) in patients with breast cancer and prostate cancer can be used for early diagnosis of metastasis in the skeleton bones: changes in indicators are observed 6-10 months before the first radiological/ MRI signs appear. The application of simultaneously used markers of bone resorption and osteogenesis in patients with breast cancer and prostate cancer provides a sensitivity of 89.7 %, a specificity of 84.5 %, a positive predictive value of 82.6 % and a negative predictive value of 95.3 %.

Prognostic role of biological markers of bone metabolism in patients with coronary artery disease after coronary artery bypass grafting

Prognostic role of biological markers of bone metabolism in patients with coronary artery disease after coronary artery bypass grafting

Alterations of Bone Metabolism in Patients with Diabetes Mellitus.

Aim The study aims to develop a practical model for screening bone turnover state in patients with diabetes and evaluate its clinical usefulness to identify diabetic osteopathy. Materials The study was conducted in 2015–2017 in the Endocrinology Department of the Therapeutic Clinic of AM University. A total of 235 patients were assessed in the study (98 with T1DM and 137 with T2DM). 89 nondiabetic subjects served as controls. Bone mineral density (BMD) [by dual energy X-ray absorptiometry (DXA)] and serum markers of bone remodeling [aminoterminal propeptide of procollagen type I (P1NP) and c-terminal telopeptide of type I collagen (CTX)], parathyrin, and 25(OH)D were measured in all 235 patients. Results Our results show that patients with T2DM have lower b-CTx values and relatively higher levels of P1NP, reflecting less pronounced changes in bone metabolism compared to patients with T1DM, regardless of age or duration of the disease. Osteoporosis was detected in 50% of patients with T1DM, compared to 13% of patients with T2DM. Conclusion In some cases, bone remodeling markers are useful for improving the assessment of the state of bone tissue in early stages of diabetes, while alterations in bone microarchitecture may not always be captured by bone mineral density measurements.

The effects of bone metabolism in different methylprednisolone pulse treatments for Graves' ophthalmopathy.

The aim of the present study was to analyze the effects of methylprednisolone pulse therapy (MPPT) courses on bone metabolism in patients with Graves' ophthalmopathy (GO). A retrospective analysis of 45 patients with moderate-to-severe active GO who received 1 or 2 courses of MPPT was performed. Of these, 16 patients underwent 2 courses of treatment. Bone metabolic markers and the density of the lumbar spine (L1-4), femoral neck and total hip were measured using a dual-energy X-ray bone density instrument, and the differences in bone metabolism prior to and after treatment were determined for each group and compared. The results indicated that serum I collagen N-terminal peptide (P1NP) and serum β-collagen crosslinked C-terminal peptide (CTX) were markedly decreased after the first pulse of treatment. In those patients who received a second course of MPPT, CTX levels were significantly decreased, but P1NP was not significantly different from the baseline value. CTX and P1NP levels remained unchanged between the first and second course of MPPT; similarly, there were no changes from baseline in 25(OH) vitamin D3 and bone mineral density after the first and second course of MPPT. However, the level of 25(OH) vitamin D3 was significantly elevated after the second course compared with the first course. In conclusion, the side effects of MPPT on bone metabolism were marginal and a second course of MPPT did not worsen bone metabolism. These MPPT regimens may therefore be considered to be a safe and effective treatment option for patients with moderate-to-severe active GO.

Evaluation of the association of Wnt signaling with coronary artery calcification in patients on dialysis with severe secondary hyperparathyroidism

BackgroundPatients with end-stage renal disease have a higher risk of death from cardiovascular events, which can be mainly attributed to coronary artery calcification (CAC). Wnt signaling is involved in vascular development and may play a role in vascular calcification. This study aimed to evaluate CAC prevalence in patients on dialysis with severe secondary hyperparathyroidism (SHPT) and identify CAC risk factors.MethodsThe study is a retrospective analysis of the severe hyperparathyroidism registration study that prospectively recruited patients on dialysis with severe SHPT who were candidates for parathyroidectomy, from October 2013 to May 2015. CAC and bone mineral density (BMD) were measured. Demographic and clinical data including calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, Dickkopf-related protein 1 (DKK1), and sclerostin levels were analyzed. CAC scores were reported in Agatston units (AU).ResultsA total of 61 patients were included in this study. No CAC, mild CAC (<100 AU), moderate CAC (>100 AU), and severe CAC (>400 AU) were observed in 4.9%, 11.4%, 14.8%, and 68.9% of patients, respectively. DKK1 and sclerostin were not associated with CAC. In univariate analysis, CAC was significantly correlated with age, sex (male), total cholesterol, and intravenous pulse calcitriol (p<0.05). CAC was not inversely correlated with the BMD, T scores, or Z scores of the femoral neck (p>0.05). In multivariate analysis, the stepwise forward multiple linear regression revealed that CAC was associated with age, male sex and intravenous pulse calcitriol (p<0.05). Furthermore, serum sclerostin was positively correlated with the BMD of the femoral neck but negatively associated with intact parathyroid hormone (p<0.05). Serum sclerostin was significantly associated with severely low bone mass with Z-scores<-2.5 of the femoral neck, even when adjusted for serum intact parathyroid hormone, vitamin D status, dialysis pattern, sex, and DKK-1 (p<0.05).ConclusionsThe patients on dialysis with severe SHPT have a high prevalence of vascular calcification. Although the Wnt signaling pathway could play a role in hyperparathyroid bone disease, CAC may be mainly due to the treatment modality rather than the Wnt signaling pathway associated bone metabolism in patients on dialysis with severe SHPT.

Retrospective Analysis of Bone Metabolism in Patients on Waiting List for Simultaneous Pancreas-Kidney Transplantation.

Posttransplant osteoporosis, which evolves from preexisting bone pathologies, represents a serious complication with deteriorating consequences. The aim of our study was to evaluate epidemiological data on bone mineral density (BMD) in subjects with type 1 diabetes (T1DM) in advanced stages of diabetic nephropathy indicated for simultaneous pancreas-kidney transplantation (SPK). We retrospectively compiled biochemical and densitometrical data from 177 patients with T1DM at CKD (chronic kidney disease) stages G4-G5 (115 men, 62 women, median age 40 yr, diabetes duration 23 yr) enrolled on waiting list for SPK for the first time between the years 2011 and 2016. Median Z-scores were as follows: lumbar spine (LS): -0.8 [interquartile range -1.75 to 0.1]; total hip (TH): -1.2 [-1.75 to -0.6]; femoral neck (FN): -1.2 [-1.9 to -0.7]; and distal radius (DR): -0.8 [-1.4 to -0.1]. We noted a gender difference in LS, with worse results for men (-1.1 vs. -0.3) even after adjusting for BMI (body mass index) and glomerular filtration (p < 0.001). Osteoporotic and osteopenic ranges (based on T-scores) for all major sites were 27.7% and 56.5%, respectively, with similar results across both genders. Women had a significantly higher proportion of normal BMD in LS than men (67.7 vs. 49.4%, p < 0.05). Patients with T1DM at CKD stages G4-G5 exhibited serious BMD impairment despite their young age. Men surprisingly displayed lower Z-scores and higher percentages of pathological BMD values in LS than women did. The introduction of adequate preventive measures during the advanced stages of diabetic nephropathy to prevent bone loss is recommended.

Comparison of laboratory and imaging methods associated with bone metabolism in patients with or without renal failure under the age of 45 years with elevated parathyroid hormone levels

Objectives: Although bone biopsy is considered the gold standard for the definitive diagnosis of renal osteodystrophy; it is not suitable for routine clinical practice due to its invasive nature. The present study was aimed to evaluate and compare the bone mineral status using dual energy X-ray absorptiometry of patients with or without chronic kidney disease in young population with elevated parathyroid hormone levels. Methods: This was a single center, cross-sectional, retrospective study conducted in patients younger than 45 years of age. The study was performed in the outpatient clinic of a university hospital. Patients with elevated parathyroid hormone levels were included. Results: Among them, 29 had renal insufficiency, 158 had normal renal function. Measured bone mineral density with dual energy X-ray absorptiometry and laboratory values were collected from patient files. The primary end point was to assess the efficiacy of dual energy X-ray absorptiometry in patients with or without renal failure. Except Z score at Ward’s triangle, all of the T and Z scores at lomber, femur neck, trochanteric, and intertrochanteric areas were found significantly lower in patients with chronic kidney disease compared to those without (p &amp;lt; 0.001). Conclusion: Dual energy X-ray absorptiometry seemed to be a reliable method for detection of osteoporosis in premenopausal female and male patients younger than 45 years of age with or without renal failure with elevated parathyroid hormone levels.

MON-447 Impact Of Cortisone And Glucocorticoid Metabolites On Bone Turnover Markers in Male Patients With Hypopituitarism

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

The study of new biomarkers of bone metabolism of sclerostin and cathepsin K in patients with type 2 diabetes mellitus

BACKGROUND: Deterioration of bone tissue in type 2 diabetes mellitus (T2D): lead to the increased bone brittleness and to higher risk of low-energy fractures.&#x0D; AIM: to study serum levels of sclerostin and cathepsin K in assessing bone metabolism in patients with type 2 diabetes mellitus.&#x0D; MATERIAL AND METHODS: 102 postmenopausal women aged from 46 to 67 years were examined. All patients were divided into 4 groups: the first group included 39 patients with type 2 diabetes (T2DM) and postmenopausal osteoporosis (PO), the second group — 25 patients with PO without T2DM, the third group included 21 patients with T2DM but without PO, and the fourth group (control) — 17 people. Patinets of all groups were tested for ionized calcium, phosphorus, total alkaline phosphatase (ALP), parathyroid hormone, 25 (OH) vitamin D, bone mineral density in groups I, II, and IV, levels of sclerostin and cathepsin Kin seru, were also obtained.&#x0D; RESULTS: No statistically significant differences have been observed between groups in sclerostin levels, a positive correlation was found between sclerostin and НbА1с (r=0.43; p=0.009) in the group of patients with T2DM and PO, a negative correlation was found between sclerostin and ionized calcium (r=–0.45; p=0.037) in the group of patients with PO. Cathepsin C in the first group was lower than in the second group (p=0.046), but taking into account Bonferroni correction this difference was not statistically significant. In the first and third groups, 25 (OH) vitamin D was lower than in the groups without T2D. The ALP negatively correlated with the duration of the postmenopause (r=–0.39 and r=–0.64; р=0.05, respectively).&#x0D; CONCLUSIONS: Cathepsin С was lower in patients with T2DM2 and PO, which may indirectly indicate a decreased bone resorption. Concentration of sclerostin, which plays a key role in the mechanism of inhibiting osteoblastogenesis, positively correlated with НbА1с.

Brown tumor of the femur and ulna in a woman with hyperparathyroidism

Abstract Objective A typical brown tumor caused by hyperparathyroidism (HPT) is rare. In this report, we describe our pathological findings along with a review of the literature to enhance understanding of the disease and prevent misdiagnosis, as well as to provide evidence for treatment and prognosis. Methods We present a case of brown tumor of the left proximal femur and pelvis in a 57-year-old woman who was admitted to our hospital (Dalian Municipal Central Hospital, Dalian, China). Pelvic computed tomography (CT) showed cystic expansile lesions in the left proximal femur and pelvis. Lung and abdominal CT also revealed multiple lytic lesions in the ribs and lumbar spine. X-ray of the left ulna and radius showed that the middle of the left ulna had a fracture caused by a brown tumor. A bone biopsy from the left proximal femur showed focal distribution of giant cells, with hemorrhage and fibrin hyperplasia. Results The patient underwent internal fixation of the left intertrochanteric fracture, and postoperative bone biopsy showed focal distribution of giant cells with hemorrhage and fibrin hyperplasia. The patient had a parathyroidectomy 5 months after discharge. Two weeks later, the patient developed a fracture in the right femoral neck and pain in the left forearm. X-ray of the left ulna and radius showed that the middle of the left ulna was affected by a pathological fracture caused by a brown tumor. The patient was debilitated and declined surgical treatment. The patient and her family chose discharge. Conclusion Brown tumor of bone, also called osteitis fibrosa cystica, is a rare non-neoplastic lesion that reflects abnormal bone metabolism in patients with HPT. However, with fine needle aspiration cytology in combination with biochemical tests, a correct diagnosis can be reached. The increase in osteoclast activity leads to decalcification and dissolution of bone, and formation of a cystic bone defect with hyperplastic fibrous tissue. This eventually becomes a brown tumor, with deformed and bleeding fibrous tissue. The patient had a typical brown tumor, as well as osteoporosis, anemia, and pathological fractures.

Indicators of markers of bone metabolism in patients with generalized periodontitis depending on blood group

Indicators of markers of bone metabolism in patients with generalized periodontitis depending on blood group

An analysis of biochemical markers of bone metabolism in patients with idiopathic benign paroxysmal positional vertigo

Objective:To analyze the biochemical markers of bone metabolism in patients with idiopathic benign paroxysmal positional vertigo（iBPPV）. Method:The study included 38 patients with iBPPV. Thirty-two healthy persons were collected as control group. Routine history collection, physical examination, and diagnosis were recorded in case group. Both the case group and control group were assessed for the status of bone biochemical markers. Result:①Among the 38 patients with iBPPV, posterior semicircular canal BPPV in right ear（R-PC-BPPV）presented in 23 cases , left ear（L-PC-BPPV）in 9 cases, horizontal semicircular canal BPPV in right ear in 2 cases, and in left ear in 2 cases, horizontal semicircular canal cupulolithiasis in 2 cases. ②The value of osteocalcin(OC), 25 hydroxyvitamin D3［25(OH)D3］, amino terminal propeptide of type I procollagen (PINP) in case group were lower than the normal reference value, and also significantly lower than that in the control group,OC: t=-2.013, P=0.048; 25(OH)D3: t=-2.133，P=0.037; PINP: t=-2.615,P=0.011. There was no significant difference of β-isomerized carboxy-terminal telopeptide of type I collagen (β-CTx) between the case group and control group. ③The value of OC(t=-2.187，P=0.035), 25(OH)D3(t=-2.190，P=0.035) and PINP(t=-2.322，P=0.026) in patients lower than 50 years old were significantly lower than that in the control group. The difference of these biochemical markers between the case and control group was not significant when subjects were ≥50 years old. Conclusion:The biochemical markers of bone metabolism in patients with iBPPV are declined, especially in patients lower than 50 years old. There may be abnormal bone metabolism in iBPPV patients.

Dynamics of indicators of oxidative stress and bone metabolism during treatment with thiotriazolin in patients with combined type 2 diabetes mellitus and osteoporosis course who reside in anthropogenic pressure conditions

The aim of the study. To investigate the effect of thiotriazolin on oxidative stress and bone metabolism in patients with a combined course of type 2 diabetes and osteoporosis, who permanently reside in industrial region.Materials and methods. On the basis of the educational and scientific medical center University Hospital of Zaporizhzhia State Medical University, 44 patients with combined course of type 2 diabetes and osteoporosis, who permanently resided in Zaporizhzhia, were examined for the period from 2016–2017. 22 patients received standard basic therapy for type 2 diabetes and osteoporosis, and 22 patients additionally received thiotriazolin. Patient groups were comparable in age, sex, and duration of type 2 diabetes mellitus. All patients studied the concentration of markers of oxidative stress (nitrotyrosine, 8-hydroxyguanine) and bone metabolism (osteocalcin and deoxypyridinoline).Results. Patients with a combined course of type 2 diabetes mellitus and osteoporosis who received basic therapy with thiotriazolin supplementation registered a significant decrease in the concentration of oxidative stress. Thus, in patients of the second group, there was a significant decrease in the serum level of nitrotyrosine by 5.5 times (pl0.05) and 8-hydroxyguanine by 2.1 times (pl0.05). When evaluating markers of bone metabolism in patients of the second group, the level of osteocalcin increased by 24 % (pl0.05), and the concentration of deoxypyridinoline significantly decreased in individuals of both groups, but in the group with the addition of thiotriazolin, its rate decreased by 30%, and in the first group only 16 % (pl0.05).Conclusions. In patients with a combined course of type 2 diabetes and osteoporosis, which, in addition to basic therapy, thiotriazolin was included, a significant decrease in markers of oxidative stress was registered in a daily dose of 600 mg for 3 months. Under the influence of basic therapy with the addition of thiotrazoline, a significant increase in bone formation and a decrease in bone resorption were observed in patients with a combined course of type 2 diabetes and osteoporosis

Influence of antiretroviral therapy on bone metabolism of patients with chronic hepatitis B: a review.

Hepatitis B is a major public health problem worldwide and associated with significant mortality. To prevent or delay the deleterious effects of chronic infection by the hepatitis B virus, patients should be carefully followed, and antiviral therapy indicated according to specific recommendations. Currently, available drugs inhibit viral replication and slow or stop the progression of inflammation and fibrosis of the liver. However, the drugs for oral use in the treatment of hepatitis B, jointly referred to as nucleoside/nucleotide analogs, are indicated for prolonged use and have potential side effects. The reduction in bone mineral density was associated with the use of tenofovir, already evaluated in patients infected with HIV because the drug is also part of the therapeutic arsenal for this viral infection. There are few studies on the effects of tenofovir in patients with mono hepatitis B. Therefore, this literature review proposes to examine how hepatitis B acts in the body and the mechanisms by which antiretroviral drugs (especially tenofovir) can affect bone metabolism.

The level of bone metabolism in patients with dental implants

The aim of the study was to determine the activity of alkaline phosphatase (AP), tartrate-resistant acid phosphatase (TRAP) and osteocalcin in oral fluid (OF) in patients with dental implants. Dental intraosseous implantation was performed in 164 patients, aged 45 to 60 years (mean age 54.6±4.17 years), 78 (47.6%) males and 86 (52.4%) females. In 75.6% of patients more than 3 teeth were absent. A total of 641 screw intraosseous implants of the MIS system were installed. Studies were performed prior to implant placement, at 7, 14, 21 days and 3 and 6 months. The control group consisted of 20 volunteers of comparable age, 9 (45.0%) males and 11 (55.0%) females. An increased activity of AP and TPAP was revealed, but the activity change of AP in comparison with the control group was not statistically significant. Activity of TRAP in patients before implantation was higher than in controls by 40.5% (p<0.05) in group without complications and by 61.9% (p<0.05) in patients with mucositis. After implantation, the activity of TPAP remained elevated for 6 months, the maximum activity was observed after 14 days and was 3 times higher than at baseline (p<0.01). The amount of osteocalcin increased, especially in the complicated course after the implantation. The highest values of osteocalcin were observed 14 days after implantation. Determination of the activity of TPAP in the OF after implantation can be used as an indicator of the state of bone metabolism.

The state of bone metabolism in patients with type 2 diabetes mellitus

The aim of this work is to investigate the state of bone metabolism status and its relationship with carbohydrate metabolism in patients with type 2 diabetes. Materials and methods. 94 patients were studied, among whom the 1 st group – 22 patients with osteoporosis (OP), the 2 nd group – 22 patients with type 2 diabetes mellitus (DM), the 3 rd group – 50 patients with combined course of these diseases. An ultrasound densitometry using the Omnisense 7000 ultrasound densitometer (BeamMed Ltd, Israel) was performed for all the patients. The state of bone tissue was determined by criteria of the WHO. The levels of osteocalcin (OC), parathyroid hormone (PTH), calcitonin in blood serum, the level of deoxypyridinoline (DPD) were determined in morning urine for all patients. In patients with type 2 DM the levels of C-peptide, insulin, glucose, HbA1c and HOMA index were studied Results. It was revealed that patients of the 3 rd group had signifiant decrease in OC level by 44 %, DPD by 24 %, PHT by 28 % (P < 0.05) in comparison to the patients of the 1 st group. In 53 % of patients of the 3 rd group the development of OP was characterized by decreased bone formation and increased bone resorption. The patients of the 3 rd group had signifiantly higher levels of Hb1c by 11.5 %, glucose by 25 %, HOMA index by 7.2 % (P < 0.05), while the level of OC and DPD were lower by 8.5 % and 17 %, (P < 0.05) respectively in comparison with patients of group 2. The levels of OC and DPD were signifiantly lower in patients with decompensation of type 2 diabetes, in comparison with compensated diabetes by -12 % and -17 %, respectively (P < 0.05). The level of HbA1c signifiantly inflences the state of bone metabolism. With an increase in HbA1c of more than 7.5 %, the level of OC decreases by 12 %, and DPD by 17 % (P < 0.05). Conclusions. The results suggest that type 2 DM leads to slowdown of bone metabolism, as the 3 rd group patients had signifiantly reduced levels of OK and DPD as compared to the patients of the 1 st group. Poor glycemic control can be one of the factors that reduce the level of bone markers.

Trabecular Bone Score (TBS) and Bone Metabolism in Patients Affected with Type 1 Neurofibromatosis (NF1)

In patients with neurofibromatosis type 1 (NF1), decreased bone mineral density (BMD) and low levels of 25-hydroxy vitamin D3 (25OHD) have been reported. Recently, the trabecular bone score (TBS) measurement has been proposed as index of bone microarchitecture and fracture risk. In 74 NF1 patients (48 females, 26 males, age 41 ± 12), we measured TBS and investigated clinical stage, lifestyle, vitamin D, serum bone turnover markers, vertebral and femoral BMD. A homogenous cohort of 61 healthy subjects was used as control group. TBS was lower in NF1 patients (1.266 ± 0.113 vs. 1.346 ± 0.105) without differences between sexes. No correlations with 25OHD, low exercise, low calcium intake, reduced sun exposure, and number of skin neurofibromas were observed. As expected, hypovitaminosis D was common (98.6%), as well as BMD reduction in hip and spine sites: In NF1 patients, bone texture evaluated by TBS was low in both sexes without any correlation with clinical or metabolic parameters, suggesting a direct role of the fibromin mutation.

The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial

BackgroundBreast cancer and its treatments are associated with a detrimental effect on bone health. Here we report the results of an exploratory analysis assessing changes in levels of biomarkers of bone metabolism in patients enrolled in the phase IIIb 4EVER study. MethodsThe 4EVER trial investigated everolimus in combination with exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. In this prespecified exploratory analysis, changes in biomarkers of bone turnover were assessed in patients from baseline to weeks 4, 12, and 24. The serum bone markers assessed were procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25-OH-vitamin D). On-treatment changes in bone markers over time were described per subgroup of interest and efficacy outcomes. ResultsBone marker data were available for 241 of 299 enrolled patients. At the final assessment, P1NP, osteocalcin, PTH, 25-OH-vitamin D (all P < 0.001), and CTX (P = 0.036) were significantly decreased from baseline values per the Wilcoxon signed-rank test. At the last assessment (24 weeks or earlier), levels of serum CTX and PTH were significantly lower (P = 0.009 and P = 0.034, respectively) among patients with vs. without prior antiresorptive treatment (ART). Serum CTX levels were significantly lower (P < 0.001), and 25-OH-vitamin D concentrations significantly higher (P = 0.029), at the last postbaseline assessment in patients receiving concomitant ART vs. those without ART. Changes from baseline in PTH and 25-OH-vitamin D concentrations to the final assessment were significantly smaller in patients with prior ART. Lower baseline serum concentrations of osteocalcin and PTH were associated with clinical response (partial vs. non-response) at 24 weeks. High serum levels of CTX and P1NP at baseline were risk factors for progression at 12 weeks. ConclusionsThese exploratory analyses support use of everolimus plus exemestane for the treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, and add to the body of evidence suggesting a potentially favorable impact of everolimus on bone turnover. Trial registrationNCT01626222. Registered 22 June 2012, https://clinicaltrials.gov/ct2/show/NCT01626222.