Biochemical Markers Of Bone Remodeling Research Articles

The difficulties of diagnosing and determining the tactics of treating osteoporosis in severe spinal scoliosis case

A female patient with early surgical menopause and severe S-shaped scoliosis was diagnosed with osteoporosis at the place of residence and treated with a bisphosphonate (zoledronic acid). Despite the deformity of the spine and chest, the patient had no complaints until recently and led an active lifestyle. During X-ray densitometry at the National Medical Research Center for Therapy and Preventive Medicine, in particular when examining the lumbar spine, there were difficulties with positioning the patient for correct scanning of the area of interest and, as a result, obtaining information about the true state of trabecular bone tissue. Bone mineral density (BMD) in the proximal femur was consistent with osteopenia. Additional laboratory and instrumental parameters, such as biochemical markers of bone remodelling (osteocalcin and C-terminal type 1 collagen telopeptide) and trabecular bone score (TBS), also did not allow to precise the risk of fractures and make an unambiguous conclusion about the necessity of continuing antiresorptive therapy. Given the low BMD values in lumbar spine (T-score -4.8 SD) and the possibility of developing vertebral compression fractures as a result of minimal trauma with further chest deformity progression and vital organs failure, it was decided to continue treatment with zoledronic acid. Further therapeutic tactics will be determined after the next scheduled examination in 1 year.

Oral health, periodontal phenotype in patients with different mineral density (morphotypes) of bone tissue

Background. Studying the systemic influence of bone mineral density (BMD) and bone turnover on oral health and periodontal phenotype is relevant for predicting the course of periodontitis and making clinical decisions to achieve good treatment results. The purpose of the research is to study the oral health, periodontal phenotype, and bone metabolism depending on the BMD of the skeleton. Material and methods. One hundred and thirty-eight patients were examined and divided into three study groups depending on the BMD (Z-score): group І — increased BMD ­(Z-score > +1 SD), group ІІ (Z-score from +1 to –1 SD), group ІІІ (Z-score < –1 SD). The state of oral health, the severity and course of periodontal diseases, the peculiarities of bone metabolism according to biochemical markers of bone remodeling, and the BMD according to the results of dual-photon densitometry were determined. Results. Reduced bone turnover, resulting in decreased serum osteocalcin (18.96 ± 1.87 ng/ml in men and 19.11 ± 1.54 ng/ml in women), high level of parathyroid hormone was registered in patients with high BMD (group I). The oral health characteristics were identified, namely, the pathological tooth wear — abfraction (84.21 %) and attrition (76.31 %), the periodontal phenotype was characterized by a thick gingival biotype, mandibular exostoses, periodontitis and periodontitis were diagnosed. Increased bone turnover, active course of generalized periodontitis, thin gingival biotype, cervical caries and hyperesthesia of the dental hard tissues were registered in patients with low BMD (group III). Conclusion. The state of oral health, namely, the dental hard tissues, the periodontal phenotype has its own characteristics and are related to the morphotype of bone tissue — its BMD and bone metabolism. Such features must be taken into account when planning treatment measures for dental patients.

FC 076DIAGNOSTIC ACCURACY OF BONE TURNOVER MARKERS IN RENAL OSTEODYSTROPHY

Abstract Background and Aims A transiliac bone biopsy is the gold standard for diagnosing renal osteodystrophy, but is not recommended as part of routine clinical workup due to its invasive nature. Suitable non-invasive alternatives have yet to be established. The aim of this study was to investigate the diagnostic accuracy novel biochemical markers of bone remodeling compared to that of biointact parathyroid hormone (PTH) for bone turnover as evaluated by histomorphometry. Method Protocolled bone biopsies were performed in end-stage kidney disease patients (ESKD, n = 80) and kidney transplant recipients (n = 119). Full-length (1-84) PTH, bone-specific alkaline phosphatase (BsAP), intact N-terminal propeptide of type I collagen (P1NP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were measured. Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC). Optimal diagnostic cutoffs were established in an exploration cohort (n=100), and subsequently validated in a separate subset of patients (n=99). Results Mean age was 55±13 years, two-thirds were men (67%), and 23% had diabetes mellitus. Post-transplant eGFR was 49 [IQR 39, 59] ml/min/1.73m². Bone turnover was low in 47 (24%), normal in 119 (60%), and high in 33 (17%) patients. All biomarkers differed significantly across categories of bone turnover (p < 0.001). The AUC of biointact PTH for high turnover was 0.82 (0.73, 0.91), which was not significantly different from AUC values for BsAP, Intact P1NP, and TRAP5b (0.87, 0.90, and 0.86, respectively). AUC of biointact PTH for low turnover was 0.71 (0.63, 0.78), which was significantly lower than the values for BsAP, Intact P1NP, and TRAP5b (0.79, 0.83, and 0.79, respectively; p < 0.05, all). Calculated optimal diagnostic cutoffs in the exploration cohort are shown in Table 1. Applying these cutoffs in the validation cohort revealed high negative predictive values for both high (92 - 96%) and low (82 - 90%) bone turnover. Positive predictive values were consistently low. Conclusion The diagnostic accuracies of BsAP, Intact P1NP and TRAP5b are sufficient to rule out both high and low bone turnover in CKD. Biointact PTH shows inferior performance, particularly in kidney transplant recipients.

Bone remodeling markers and their role in oncology

Bone metastases are a common complication of cancer. Patients with bone metastases may have experienced skeletal-related events, such as hypercalcemia, pathological fractures, pain syndrome of varying intensity, spinal cord compression with negative effects on the quality of life. Current diagnostic tools have some limitations, such as high cost and limited availability in the distant areas, as well as falls negative and falls positive results. In this aspect, non-invasive sensitive markers of bone metabolism might give additional valuable information. Bone remodeling markers (N-terminal propeptide of type 1 collagen, osteocalcin, C-terminal telopeptide of type 1 collagen, etc.) have been used for a long time to predict the effectiveness of osteoporosis treatment; as additional risk factors for treatment initiation in patients with osteoporosis, in diagnostic search for secondary forms of osteoporosis; and as predictors of fracture in population studies. This review summarizes the clinically relevant biochemical markers of bone remodeling and the available evidence for their use in the metastatic bone disease in particularly in the diagnosis and prognosis of bone metastases risk and skeletal complications, predicting clinical outcomes, bone disease progression and overall survival. It has been shown that a sufficient suppression of bone remodeling biochemical markers while on treatment with bisphosphonates is associated with an improvement in survival and a decrease in the risk of skeletal complications in patients with bone metastases. New data may become a rational basis for wider use of bone metabolism markers in oncological practice. However, it is necessary to standardize and validate the determination of bone markers and verification of cut-off diagnostic values for their introduction into the routine clinical practice of patients with malignancy.

History of alendronate.

Alendronate was synthesized in 1970s in a search for inhibitors of calcification. Istituto Gentili investigators identified it as a potent inhibitor of bone resorption and obtained a patent covering its use in the treatment of osteoporosis and other disorders of excessive bone resorption in the 1980s. Merck licensed alendronate in 1988 and its pharmaceutical chemists reformulated it as a sodium salt with good solubility in a tablet that reduced its potential for esophageal irritation. Clinical trials proved that it reduced bone turnover, increased BMD and reduced the risk of vertebral fractures in postmenopausal osteoporotic women. Merck sponsored a large clinical trials that won FDA approval for treatment of osteoporosis in postmenopausal women and showed that it reduced the risk of spine and hip fractures. Its approval in the US in 1995 spurred sales of bone densitometers and BMD testing to screen for low bone mineral density and identify osteoporosis. Bone mass measurement was supported by medical society guidelines and reimbursement by Medicare and other insurers in the USA. A 70 mg weekly instead of 10 mg daily dose of alendronate produced the same effect on BMD and biochemical markers of bone remodelling with greater convenience and reduced potential for upper GI adverse events. Consequently, by 2006, about 30 million prescriptions for alendronate were written annually in the U.S. for about 15% of postmenopausal women in the U.S. Thereafter, publicity about rare but concerning atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ) along with the expiry of Merck's patent (in 2008) and cessation of their promotion of alendronate, and a decline in use of densitometry led to a steady slide in its use even among patients for whom the benefits of alendronate far outweigh its potential risks. Nevertheless, in 25years since its regulatory approval, alendronate has undoubtedly prevented millions of fractures world-wide.

Continuous decline in bone mineral density and deterioration of bone microarchitecture 7 years after Roux-en-Y gastric bypass surgery.

ObjectiveRoux-en-Y-gastric bypass (RYGB) surgery is an effective treatment for morbid obesity. A possible overlooked side effect is negative bone metabolic consequences. DesignA seven-year prospective study following ten women and seven men after RYGB (baseline mean age 43 ± 8 years, BMI 42 ± 6 kg/m2).MethodsLumbar spine and total hip bone mineral density (BMD) using dual energy x-ray absorptiometry, distal radius and tibia bone geometry, volumetric BMD, microarchitecture and finite element estimated bone strength using high-resolution peripheral quantitative CT and biochemical markers of bone remodelling were assessed at baseline, 2 and 7 years.ResultsCompared to baseline, body weight was 24 ± 10% lower after 2 years and 21 ± 11% after 7 years. During the 7 years of follow-up, radius and tibia vBMD had declined 13 ± 8% and 8 ± 7% from baseline to 2 years and further 10 ± 7% and 7 ± 8% from 2 to 7 years (all P < 0.001). At both radius and tibia, cortical thickness declined and cortical porosity increased. From baseline to 7 years, there were clear indications of deteriorations of the trabecular network with fewer, more widely spaced and more in-homogeneously distributed trabeculae in both radius and tibia. Overall, declines in estimated bone strength of 16 ± 9% in radius and 16 ± 7% in tibia were observed (both P < 0.001).ConclusionSeven years after RYGB, evidence of continuous declines in BMD and ongoing deterioration of bone microarchitecture and reduced estimated bone strength compared to baseline and 2 years post-surgery results were found. These findings emphasize the need for regular assessment of bone health in patients with prior RYGB.

Bortezomib Overcomes Poor Prognosis Conferred By High Sictp in Untreated Plasma Cell Disorders

Introduction To date, various biochemical markers of bone remodeling have been investigated in multiple myeloma (MM) patients. Serum C-terminal telopeptide of type I collagen (sICTP) is a well-known biochemical marker of bone remodeling. Although several reports showed the relationship between a high level of sICTP and poor prognosis in MM patients, little is known about the efficacy of bortezomib in high sICTP patients. In this single center retrospective study, we assessed the association between sICTP and the prognosis of plasma cell disorder patients, particularly in patients firstly treated with bortezomib-containing regimen. Methods We retrospectively reviewed untreated MM and other plasma cell disorder patients who were diagnosed at The University of Tokyo Hospital between January 2001 and December 2016. The clinical data of patients whose sICTP was measured before the start of first-line therapy were collected. Serum ICTP was measured at diagnosis in 59 patients: 56 patients with MM, 2 patients with plasmacytoma, and 1 patient with light chain amyloidosis. These patients were divided into high sICTP and low sICTP groups according to the median of sICTP level. Additionally, patients firstly treated with bortezomib-containing regimen were divided into two groups according to the median of sICTP level. Overall survival (OS) and bone fracture-free survival (FFS) were calculated from initiation of the first-line therapy using the Kaplan-Meier method and log-rank tests. Results In 59 patients, the median age was 65 years (range, 45-85 years) and median follow-up was 387 days (range, 22-2019 days). Thirty-three patients (55.9%) were male and 26 (44.1%) were female. IgG was the most frequent subtype of M-protein (58%), followed by IgA (19%), Bence Jones proteins (19%), and IgE (3%). International scoring system classified 16 (27.1%), 24 (40.7%), and 19 (32.2%) as stage I, II, and III, respectively. Levels of sICTP were high in 31 (52.5%) patients and low in 28 (47.4%) patients. The level of sICTP differed significantly (P&lt;0.01) between the groups ISS stage I, II, and III, and increased parallel with the progression of the disease. Twenty-eight (47.4%) patients were administered bortezomib-containing regimen as first-line therapy, which was consisted of BD (bortezomib + dexamethasone), VCD (bortezomib + cyclophosphamide + dexamethasone), and VMP (bortezomib + melphalan + prednisolone). The remaining 31 (52.5%) patients were administered without proteasome inhibitors as first-line therapy. Nineteen patients (32.2%) achieved at least very good partial response after first-line therapy and 9 (15%) patients fractured after start of first-line therapy. Median OS for the entire cohort was 1874 days. In the Kaplan-Meier survival analysis, high sICTP (above upper limit: 6.0 mg/l) significantly associated with worse 2-year OS (63% versus 96%, P=0.02) and worse 2-year FFS (51% versus 86%, P=0.04). Serum ICTP may be a useful marker to predict survival and future bone fracture in our cohort, and these results are consistent with previous reports. Interestingly, in the patients firstly treated with bortezomib-containing regimen, the level of sICTP had no effect on 2-year FFS (90% with high sICTP versus 100% with low sICTP, P=0.53) and 2-year OS (95% with high sICTP versus 100% with low sICTP, P=1). Conclusion In general, high sICTP is considered to be a poor prognostic factor in MM patients, and similar results were also demonstrated in our cohort. Importantly, our data suggest that bortezomib may overcome poor prognosis conferred by high sICTP in plasma cell disorder patients. Further studies based on more cases are warranted to elucidate the efficacy of bortezomib in high sICTP patients. In addition, further studies on other proteasome inhibitors, such as carfilzomib or ixazomib are also needed. Disclosures Honda: Hitachi, Ltd.: Speakers Bureau. Toyama:Bristol-Myers Squibb: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Celgene K.K.: Speakers Bureau; Daiichi Sankyo Conpany: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau. Kurokawa:Shire Japan K.K.: Speakers Bureau; Novartis Pharma K.K.: Research Funding; Daiichi Sankyo Conpany: Speakers Bureau; Pfizer Japan Inc.: Research Funding; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Celgene K.K.: Consultancy, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma Co.,Ltd.: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Yakult Honsha Company: Speakers Bureau; Bioverativ Japan ltd.: Consultancy; Chugai Pharmaceutical Company: Consultancy, Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; MSD K.K.: Consultancy, Research Funding, Speakers Bureau; Shionogi &amp; Co., Ltd: Consultancy, Honoraria; Teijin Limited: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Janssen Pharmaceutical K.K.: Speakers Bureau.

Laboratory Monitoring of Bone Tissue Remodeling after Augmentation of Impression Intraarticular Fracture with Different Types of Bone Graft.

The effects of bone graft materials on the inflammatory response and biochemical markers of bone remodeling were studied on a rabbit model of fracture augmentation with the following grafts: β-tricalcium phosphate, demineralized bone matrix, nanostructured carbon implant, and porous titanium implant made by additive 3D printing. The markers of bone remodeling and the blood system response in the postoperative period were studied. It was found that porous titanium implant and β-tricalcium phosphate induced osteogenesis and minimized osteoclastic resorption. Augmentation with nanostructured carbon implant and demineralized bone matrix stimulated the processes of osteoclastic resorption.

Osteoporosis Pathophysiology, Epidemiology, and Screening in Rheumatoid Arthritis

To review the burden of osteoporosis (OP) in rheumatoid arthritis (RA) and to describe the OP screening strategies applied in RA. RA is an inflammatory condition that predisposes patients to development of OP. OP in RA has a multifactorial pathogenesis with systemic inflammation and glucocorticoid use playing major roles. Newer studies have reported an intriguing association between RA autoantibodies and the development of OP. OP screening strategies in RA patients include clinical and vitamin D assessment, biochemical markers of bone remodeling, and bone imaging evaluations, particularly dual-energy X-ray absorptiometry (DXA). Fragility fractures are an important comorbidity of RA. OP screening strategies are both feasible and effective in RA patients and recommended by most specialty organizations. Given the considerable exposure to factors related to OP development, such as pro-inflammatory cytokines and glucocorticoid treatment, special attention should be directed to biochemical and DXA results in RA patients.

Assessment of Biochemical Markers in Two Particular Cases with Maxilary Cysts

Biochemical markers have been previously described as predictors of bone remodelling in dental disorders. Here we present 2 cases, diagnosed with inflammatory maxillary cysts in whom biochemical markers of bone remodeling have been evaluated. Clinical evaluations, radiological and laboratory tests, including histopathological examinations were performed in both patients. Laboratory test results indicated an activation of osteoblasts in both cases. Bone alkaline phosphatase (BAP) serum levels, as a marker for bone deposition, were significantly increased in both patients. In addition, differences in the cyst size and the tartrate-resistant acid phosphatase (TRACP-5b) test results have been noted in these cases. In the first case, with a cyst [ 1.5 cm in diameter, TRACP-5b serum levels were within the normal reference laboratory values, suggesting that the process of bone resorption may be slightly decreased or potentially lacking. In the second case, with a cyst ] 3 cm in diameter, TRACP-5b serum levels were 1.5 times higher than the upper limit of the normal reference laboratory values, suggesting that a process of osteolysis apparently occured. The two cases diagnosed with maxillary cyst presented differences in the size and the TRACP-5b test results. This suggest a possible correlation between TRACP-5b serum levels, bone resorption and the size of maxillary cysts. Further studies should be performed to confirm this hypothesis.

Analysing the effect of multiple sclerosis on vitamin D related biochemical markers of bone remodelling

The Irish population is at risk of vitamin D deficiency during the winter months, but the secular trend over the past 40 years is for marked improvement. Multiple sclerosis (MS) is common in Ireland with a latitudinal pattern favouring highest incidence in northern regions; MS is linked strongly with vitamin D status as a causal factor. We sought firstly to study the relationship between vitamin D status and vitamin D-related bone biochemistry, and secondly to evaluate if MS had an independent effect on vitamin D related markers of bone remodelling. Using a case-control design of 165 pairs (MS patient and matched control) residing in three different geographic regions during winter months, we measured serum 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), C-terminal telopeptide of type I collagen (CTX) and total procollagen type I amino-terminal propeptide (PINP). Given the paired case-control design, associations were explored using mixed-effects linear regression analysis with the patient-control pair as a random effect and after log transformation of 25OHD. A two-way interaction effect was tested for vitamin D status (25OHD <30nmol/L) and the presence of MS on PTH, CTX, and PINP. In the total group, just over one-third (34.5%) had 25OHD <30nmol/L. PTH was elevated in 7.6%. CTX was not elevated in any case, and PINP was elevated in 4.5%. On mixed-effects linear regression analysis after adjusting for confounders (age, sex, renal function, and serum albumin), we demonstrated the principal determinant of 25OHD was geographical location (p<0.001), of PTH was 25OHD (p<0.001), of CTX was PTH (p<0.001), and of PINP was PTH (p<0.001). MS did not have an independent effect on PTH (p=0.921), CTX (p=0.912), or PINP (p=0.495). As regards an interaction effect, the presence of MS and 25OHD <30nmol/L was not significant but tended towards having lower PTH (p=0.207). In conclusion, in Ireland in winter only a minority had any abnormality in the secondary indices of vitamin D deficiency, and MS had no independent effect on parathyroid status or bone remodelling activity.

Randomized trial comparing efficacies of zoledronate and alendronate for improving bone mineral density and inhibiting bone remodelling in women with post-menopausal osteoporosis.

Bisphosphonates are the first-line medications for treating osteoporosis. The aim of our prospective study was to compare the efficacy of zoledronate with that of alendronate in women with post-menopausal osteoporosis based on the evaluations of bone mineral density (BMD) and serum levels of biochemical markers of bone remodelling. Chinese women with post-menopausal osteoporosis were randomly assigned to the zoledronate (n = 52) or alendronate (n = 53) group, and were treated with 5 mg zoledronate intravenously once per year and 70 mg alendronate orally once per week, respectively. During a 3-year follow-up period, the lumbar spine, femoral neck and total hip were examined using dual-energy x-ray absorptiometry every 12 months to assess BMD, and the serum levels of amino-terminal propeptide of type I procollagen (P1NP) and carboxy-terminal cross-linked telopeptides of type 1 collagen (CTX) were measured to evaluate bone formation and resorption, respectively. Greater increases in BMD occurred in the zoledronate group over the 3-year follow-up period, with increases in BMD of 41·3%, 13·5% and 20·0% at the lumbar spine, femoral neck and total hip, respectively, compared with 16·9%, 5·88% and 8·93% in the alendronate group, respectively (P < 0·05 for all). At the 3-year follow-up, P1NP and β-CTX levels were reduced by 42·1% and 50·5% in the zoledronate group, respectively, whereas the levels of each were reduced by 19·5% and 19·4% in the alendronate group, respectively (P < 0·05 for all). Once yearly zoledronate administered intravenously was more efficacious for improving BMD and reducing the serum levels of P1NP and β-CTX in Chinese women with post-menopausal osteoporosis than alendronate administered orally once per week. The incidence of adverse events after the second and third zoledronate treatments was substantially lower than that in the alendronate group, suggesting a substantially lower risk of adverse events with long-term use of zoledronate in Chinese women, compared with that of alendronate use.

Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.

Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P < .001) and cortical bone density (-5%, P < .05) and reduced cortical thickness (-15%, P < .001), whereas hypothyroid mice showed a higher trabecular bone density (+26%, P < .001) with unchanged cortical bone parameters. Histomorphometry and biochemical markers of bone remodeling indicated high bone turnover in hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P < .001) and increased in hypothyroid mice (+18%, P < .01). The increase of the number of DKK1-positive cells in hypothyroid mice was confirmed at the tissue level. Interestingly, sclerostin was increased in both disease models, although to a higher extent in hyperthyroid mice (+50%, P < .001, and +24%, P < .05). Serum sclerostin concentrations adjusted for bone mass were increased by 3.3-fold in hyperthyroid (P < .001) but not in hypothyroid mice. Consistently, sclerostin mRNA expression and the number of sclerostin-positive cells were increased in hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets.

Biochemical markers of bone metastasis

Bone metastasis is one of the most frequent and dangerous complications of malignant tumors. The last years, achievements in the study of bone remodeling mechanisms promoted the search of sensitive and specific criteria reflecting the intensity of osteolysis and osteosynthesis in bone metastatic lesions. The most informative and clinically valid biochemical markers of bone formation and resorption are characterized in this review. The data on their possible implications in diagnostics, monitoring and prognosis of skeletal lesions by various malignant tumors are presented. The attention to biochemical markers of bone remodeling as noninvasive methods for oncologic patients examination is gradually increasing with adoption of modern laboratory technologies to clinical practice. The last years, publications suggest the possibility of their use both for monitoring, prognosis and early diagnostics of bone metastasis. We present the results of our own investigation of serum C-telopeptide of type I collagen (СТX) as bone resorption marker and bone-specific alkaline phosphatase (BAP) as formation marker in 238 breast cancer patients using ELISA methods. The elevation of studied biochemical parameters in breast cancer patients was significantly associated with the extent of skeletal metastases (р &lt; 0.02–0.00001), pathological fractures (р &lt; 0.005–0.0001) and the severity of pain (р &lt; 0.01–0.00002). Elevated rate of bone turnover was associated with reduced overall survival of breast cancer patients. The significant difference of overall survival estimated on a base of cut-off values of CTX (0.74 ng/ml) and BAP (43.7 IU/L) was found both in the groups of breast cancer patients with and without bone metastases. Serum СТХ and BAP are of value in monitoring and predicting the status of breast cancer bone metastases.

Biochemical markers of bone metastasis

Bone metastasis is one of the most frequent and dangerous complications of malignant tumors. The last years, achievements in the study of bone remodeling mechanisms promoted the search of sensitive and specific criteria reflecting the intensity of osteolysis and osteosynthesis in bone metastatic lesions. The most informative and clinically valid biochemical markers of bone formation and resorption are characterized in this review. The data on their possible implications in diagnostics, monitoring and prognosis of skeletal lesions by various malignant tumors are presented. The attention to biochemical markers of bone remodeling as noninvasive methods for oncologic patients examination is gradually increasing with adoption of modern laboratory technologies to clinical practice. The last years, publications suggest the possibility of their use both for monitoring, prognosis and early diagnostics of bone metastasis. We present the results of our own investigation of serum C-telopeptide of type I collagen (СТX) as bone resorption marker and bone-specific alkaline phosphatase (BAP) as formation marker in 238 breast cancer patients using ELISA methods. The elevation of studied biochemical parameters in breast cancer patients was significantly associated with the extent of skeletal metastases (р < 0.02–0.00001), pathological fractures (р < 0.005–0.0001) and the severity of pain (р < 0.01–0.00002). Elevated rate of bone turnover was associated with reduced overall survival of breast cancer patients. The significant difference of overall survival estimated on a base of cut-off values of CTX (0.74 ng/ml) and BAP (43.7 IU/L) was found both in the groups of breast cancer patients with and without bone metastases. Serum СТХ and BAP are of value in monitoring and predicting the status of breast cancer bone metastases.

Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: a randomized, double-blind, placebo-controlled, crossover trial.

Creatine supplementation has emerged as a promising non-pharmacological therapeutic strategy to counteract muscle dysfunction and low lean mass in a variety of conditions, including in pediatric and rheumatic diseases. The objective of this study was to examine the efficacy and safety of creatine supplementation in childhood systemic lupus erythematosus (C-SLE). C-SLE patients with mild disease activity (n = 15) received placebo or creatine supplementation in a randomized fashion using a crossover, double-blind, repeated-measures design. The participants were assessed at baseline and after 12 weeks in each arm, interspersed by an eight-week washout period. The primary outcomes were muscle function, as assessed by a battery of tests including one-maximum repetition (1-RM) tests, the timed-up-and-go test, the timed-stands test, and the handgrip test. Secondary outcomes included body composition, biochemical markers of bone remodeling, aerobic conditioning, quality of life, and physical capacity. Possible differences in dietary intake were assessed by three 24-hour dietary recalls. Muscle phosphorylcreatine content was measured through phosphorus magnetic resonance spectroscopy (31 P-MRS). The safety of the intervention was assessed by laboratory parameters, and kidney function was measured by (51)Cr-EDTA clearance. Additionally, self-reported adverse events were recorded throughout the trial. Intramuscular phosphorylcreatine content was not significantly different between creatine and placebo before or after the intervention (creatine-Pre: 20.5 ± 2.6, Post: 20.4 ± 4.1, placebo-Pre: 19.8 ± 2.0; Post: 20.2 ± 3.2 mmol/kg wet muscle; p = 0.70 for interaction between conditions). In addition, probably as a consequence of the lack of change in intramuscular phosphorylcreatine content, there were no significant changes between placebo and creatine for any muscle function and aerobic conditioning parameters, lean mass, fat mass, bone mass, and quality of life scores (p > 0.05). The (51)Cr-EDTA clearance was not altered by creatine supplementation and no side effects were noticed. A 12-week creatine supplementation protocol at 0.1 g/kg/d is well tolerated and free of adverse effects but did not affect intramuscular phosphorylcreatine, muscle function, free-fat mass or quality of life in non-active C-SLE patients. Clinicaltrials.gov number: NCT01217320.

Association entre les marqueurs du remodelage osseux, la densité minérale osseuse et le statut vitaminique D chez des femmes ménopausées d’origine marocaine

The aim of the study is to find the correlation between bone turnover markers and bone mineral density in a cohort of Moroccan postmenopausal women. Patients and methodsA cross-sectional study, conducted over a period of 12 months from October 2008 to November 2009. Five hundred Moroccan postmenopausal women volunteers participated in this study and we included only 185. ResultsIn this cohort of 185 women, average age 60years, the percentage of osteoporotic women was 35.7%, they were older 62.09 (9.13) years and they had an average of the body mass index (BMI), the lowest 29.58 (4.45). The values of the bone mineral density (BMD) measured at the lumbar spine correlated positively and significantly with BMI (P<0.001), serum calcium (P=0.026), negatively with age (P<0.001) and osteocalcin (OC) (P=0.0033). As for the results of BMD measured at the femoral neck, they show a negative and highly significant correlation with age (P<0.001) and osteocalcin. Looking for an association between the biochemical markers of bone remodeling, a weak positive correlation was found between the calcium (Ca) and alkaline phosphatase (PAL) on the one hand and Ca and intact parathyroid hormone (PTHi) in the other hand. And a significant positive correlation was found between PTHi and PAL, and between PTHi and OC. Finally, a significant positive correlation was found between the cross-laps (β-CTX) and Ca and between PAL and OC. ConclusionOur results are in agree to some international studies and disagree to others.

The Association of Serum Osteocalcin with the Bone Mineral Density in Post Menopausal Women

The markers of bone remodelling, such as serum osteocalcin, may be used to assess osteoporosis and to predict the fracture risk in elderly persons, especially in women. The bone mineral density which reflects the bone mass and strength, also predicts osteoporotic related hip fractures. So, this work highlights the association between the bone turnover and the bone mass and strength. To assess the association between the biochemical markers of bone remodeling and osteocalcin with the bone mineral density in non osteoporotic and osteoporotic women among post menopausal subjects. Sixty postmenopausal women whose ages ranged from 55-65 years included in this study, were further divided into group 1 (thirty non osteoporotic subjects) and group 2 (thirty osteoporotic subjects). For all the subjects, serum osteocalcin was measured by ELISA. BMD was measured by the Dual Energy X- Ray Absorptiometry (DXA) scan. The women with osteoporosis were diagnosed, based on the T- score of the bone mineral density, by the DXA scan. The Student's "t" test was performed between the variables of both the groups and a correlation test was also performed between osteocalcin and BMD by using SPSS. A negative correlation was found between the osteocalcin level and the bone mineral density in post menopausal women. The mean values of both serum osteocalcin and BMD between the osteoporotic and the non osteoporotic subjects were statistically significant. An increased bone turnover coincides with the trabecular deterioration in osteoporotic women of the post menopausal age group. A combination of biochemical markers and BMD may be a better predictor of the fracture risk than when it was assessed by either alone. The biochemical markers of the bone turnover cannot be a substitute for the serial BMD measurement, but they may be useful when they are considered in conjunction with the BMD measurement.

Bone formation and resorption markers as diagnostic tools for bone metastases evaluation

Bone metastases are a frequent complication of several types of cancers. Since bone metastases are difficult to diagnose with the current available approaches, there is a demand for new methods for assessing bone response. In this context, biochemical markers of bone remodeling may provide useful information on bone turnover that, in turn, may reflect disease activity in bone. In this study we tested a panel of bone remodeling markers (distinguishing between bone formation and bone resorption ones) in different groups of cancer patients, so as to evaluate the potential clinical role of the examined bone remodeling markers in the early diagnosis of metastases formation and progression. Among the bone resorption markers, tartrate resistant acid phosphatase 5b (TRAP5b) resulted the most specific for the metastatic tumor stage. Both the bone formation markers we analyzed displayed a direct correlation (positive for bone-specific alkaline phosphatase [BAP] and negative for osteocalcin [OC]) with tumor disease progression, ranging from healthy controls to primary tumor and, ultimately, to the metastatic stage. Taken together our results suggest that these markers can be valuable tools to be used, in parallel with traditional methods of metastases diagnosis, in order to monitor more in detail the pathological effect of metastases progression in bone tissue.

EFFECT OF ZOLEDRONIC AND IBANDRONIC ACIDS ON BONE METABOLISM IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS

In open prospective study we determine the efficacy of zoledronic and ibandronic acids on bone metabolism markers and bone mineral density in women with postmenopausal osteoporosis. 225 women with postmenopausal osteoporosis treated with zoledronic acid in dose 5 mg, intravenously, once a year and 64 women treated ibandronic acid were followed up. The investigators assessed clinical and medical history data, evaluated the gynecological and somatic statuses, and made laboratory and instrumental studies: clinical, biochemical blood tests, general urinalysis, determination of serum bone metabolism markers (B-Crosslaps, osteocalcin), osteodensitometry and electrocardiography, therapist ’s examination if needed. Therapy with zoledronic acid 5 mg once a year and ibandronic acid 150 mg once a month was followed by a significant reduction in resorption markers (B-Crosslaps) just following one month. Formation markers decreased to a lesser degree, which was indicative of preserved positive bone remodeling balance during the therapy. Determination of biochemical markers of bone remodeling permits assessment of an individual patient response to antiresorbtive therapy just in the first month after infusion. Zoledronic acid or ibandronic acid therapy exerts a rapid and potent effect on bone metabolism, mainly by inhibiting the resorption processes.