A Prospective Study on Critical Illness and Changes in Bone Turnover in Adult Patients

Critical illness has been recognized to acutely influence bone metabolism and, consequently, bone mineral density. The main purpose of this study was to describe bone metabolism changes in adult survivors of critical illness in the attempt to correlate changes with severity scores. It is an open, prospective, observational, monocentric study on patients admitted to the ICU was conducted, evaluating bone metabolism at baseline (within 72 hours of ICU admission), 6 months, and 12 months. Fifty-nine patients admitted to the ICU (63% males), mean age 58 ± 16 years, were enrolled. Of these, 20 patients (34%) completed the one-year follow up. At baseline, bone resorption showed an increase, which was maintained at 6 months, with normalization at 12 months. Patients showed, in a majority of cases, hypovitaminosis D with hyperparathyroidism at baseline with subsequent normalization. A trend towards a correlation was described between severity scores and serum 25(OH) vitamin D and bone turnover marker levels. These results contribute to the confirmation of a positive association between critical illness requiring ICU and bone metabolism changes. This study poses the bases for further studies to evaluate bone health in ICU patients.

Butyrate Inhibits Osteoclast Activity In Vitro and Regulates Systemic Inflammation and Bone Healing in a Murine Osteotomy Model Compared to Antibiotic-Treated Mice

Short-chain fatty acids (SCFAs) produced by the gut microbiota have previously been demonstrated to play a role in numerous chronic inflammatory diseases and to be key mediators in the gut-bone signaling axis. However, the role of SCFAs in bone fracture healing and its impact on systemic inflammation during the regeneration process has not been extensively investigated yet. The aim of this study was to first determine the effects of the SCFA butyrate on key cells involved in fracture healing in vitro, namely, osteoclasts and mesenchymal stromal cells (MSCs), and second, to assess if butyrate supplementation or antibiotic therapy impacts bone healing, systemic immune status, and inflammation levels in a murine osteotomy model. Butyrate significantly reduced osteoclast formation and resorption activity in a dose-dependent manner and displayed a trend for increased calcium deposits in MSC cultures. Numerous genes associated with osteoclast differentiation were differentially expressed in osteoclast precursor cells upon butyrate exposure. In vivo, antibiotic-treated mice showed reduced SCFA levels in the cecum, as well as a distinct gut microbiome composition. Furthermore, circulating proinflammatory TNFα, IL-17a, and IL-17f levels, and bone preserving osteoprotegerin (OPG), were increased in antibiotic-treated mice compared to controls. Antibiotic-treated mice also displayed a trend towards delayed bone healing as revealed by reduced mineral apposition at the defect site and higher circulating levels of the bone turnover marker PINP. Butyrate supplementation resulted in a lower abundance of monocyte/macrophages in the bone marrow, as well as reduced circulating proinflammatory IL-6 levels compared to antibiotic- and control-treated mice. In conclusion, this study supports our hypothesis that SCFAs, in particular butyrate, are important contributors to successful bone healing by modulating key cells involved in fracture healing as well as systemic inflammation and immune responses.

Serum and Urinary Osteocalcin in Healthy 7- to 19-Year-Old Finnish Children and Adolescents

Children and adolescents have high bone turnover marker (BTM) levels due to high growth velocity and rapid bone turnover. Pediatric normative values for BTMs reflecting bone formation and resorption are vital for timely assessment of healthy bone turnover, investigating skeletal diseases, or monitoring treatment outcomes. Optimally, clinically feasible measurement protocols for BTMs would be validated and measurable in both urine and serum. We aimed to (a) establish sex- and age-specific reference intervals for urinary and serum total and carboxylated osteocalcin (OC) in 7- to 19-year-old healthy Finnish children and adolescents (n = 172), (b) validate these against standardized serum and urinary BTMs, and (c) assess the impact of anthropometry, pubertal status, and body composition on the OC values. All OC values in addition to other BTMs increased with puberty and correlated with pubertal growth, which occurred and declined earlier in girls than in boys. The mean serum total and carboxylated OC and urinary OC values and percentiles for sex-specific age categories and pubertal stages were established. Correlation between serum and urinary OC was weak, especially in younger boys, but improved with increasing age. The independent determinants for OC varied, the urinary OC being the most robust while age, height, weight, and plasma parathyroid hormone (PTH) influenced serum total and carboxylated OC values. Body composition parameters had no influence on any of the OC values. In children and adolescents, circulating and urinary OC reflect more accurately growth status than bone mineral density (BMD) or body composition. Thus, validity of OC, similar to other BTMs, as a single marker of bone turnover, remains limited. Yet, serum and urinary OC similarly to other BTMs provide a valuable supplementary tool when assessing longitudinal changes in bone health with repeat measurements, in combination with other clinically relevant parameters.

Effects of palliative radiotherapy and bisphosphonate usage on bone turnover marker levels in cancer patients with osteolytic bone metastases

Objectives: In this study, we aimed to investigate the bone turnover marker levels according to bisphosphonate usage and radiotherapy (RT) in cancer patients with metastases in osteolytic pattern. Patients and methods: A total of 52 patients (13 males, 39 females; median age: 52 years; range, 37 to 78 years) treated with RT for osteolytic bone metastases between April 2005 and April 2006 were retrospectively analyzed. Bone-specific alkaline phosphatase (BAP), amino-terminal cross-linked telopeptide of type I collagen (NTX-I), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OC), deoxypyridinoline (DPD), pyridinoline (PYD), alkaline phosphatase (ALP), creatinine, calcium (Ca), phosphate (P), magnesium (Mg), and 24-h urine Ca levels were measured in blood and urine before the initiation of RT, six weeks and six months after RT. Results: A decrease in BAP, PINP, and creatinine levels was observed after RT (Week 6 p=0.006, Month 6 p=0.008). Sixteen patients who already used bisphosphonate before RT were excluded from statistical calculation. The remaining 36 patients who were treated with bisphosphonate after the first blood test were evaluated separately. In this group of patients, BAP, PINP, NTX, creatinine, and Ca levels significantly increased at six weeks after RT. The PINP and creatinine values significantly decreased at six months after RT. The variation between two different RT arms was assessed with repeated measures variance analysis. There was a statistically significant difference for NTX, OC, and creatinine levels between the first and second measurements. Conclusion: Radiotherapy is an effective method in the treatment of osteolytic bone metastases. Bone turnover markers can provide an objective evaluation on RT response and parallel to imaging modalities criteria for evaluation. Bisphosphonates may alter the levels of these indicators. However, in this study, there were no statistically significant differences between the levels of markers for two different RT schedules.

Prevalence of vitamin D inadequacy and bone turnover markers concerning bone mineral density in older persons

Owing to the early tooth loss in a large population, the need for removable prosthodontic therapy has widely increased. Loss of teeth can occur due to trauma, periodontal disease, dental caries, and/or oral health negligence. The removable prosthesis is preferred over other teeth replacement methods owing to its cost-effectiveness. However, due to continuous alveolar bone resorption, relining of the removable prosthesis is needed regularly. We aimed to assess the prevalence of vitamin D deficiency and bone turnover marker concerning bone mineral density. Eighty complete denture wearers either in the maxilla or in the mandible or both constituted the study sample. Before the study, all subjects were explained the procedures of the study, and informed consent was obtained before proceeding with the study. Subjects were instructed to provide an early morning sample in a fasting state as serum osteocalcin (OCN) and C-terminal telopeptide (C-Tx) have diurnal variations. Blood samples were collected, and samples were ruled out for 25-OH vitamin D, serum OCN, and C-TX. To determine the association between frequency of relining and bone turnover marker, the collected data were subjected to statistical evaluation. Significant correlations were seen between bone C-Tx, turnover markers (p<0.001), and frequency of denture relining and osteocalcin (p<0.001). No statistically significant effect of gender, vitamin D levels, age, calcium levels, vitamin D supplements, and diabetes was seen on denture relining frequency. The present study concludes that an elevated level of the bone turnover markers such as OCN and C-Tx increases the frequency of relining.

Effects of Soy Isoflavones on Biochemical Markers of Bone Metabolism in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

This systematic review and meta-analysis of randomized controlled trials was performed to more completely assess potential changes in bone turnover marker levels in postmenopausal women during the intake of soy isoflavones. PubMed (Medline) and EMBASE were searched for relevant studies, and their quality was evaluated according to Cochrane criteria. The levels of markers were evaluated in a total of 1114 women who ingested mean daily doses of 98.2 mg (30.9 to 300) of soy isoflavones for 3 to 24 months, in comparison to those of 1081 subjects who used a placebo. Ten, eighteen, eight, and fourteen comparison studies were finally selected for an estimation of the effects on osteocalcin (OC), bone alkaline phosphatase (BAP), pyridinoline (PYD), and deoxypyridinoline (DPD), respectively. A summary of the results of intervention was as follows: 4.16%, 95% CI: –7.72–16.04, p = 0.49 for OC; 5.50%, 95% CI: –3.81–14.82, p = 0.25 for BAP; –12.09%, 95% CI: –25.37–1.20, p = 0.07 for PYD; and –7.48%, 95% CI: –15.37–0.41, p = 0.06 for DPD. The meta-analysis of the included studies revealed some statistically insignificant observations that soy isoflavones intake is associated with a trend in increased levels of OC and BAP, as well as a trend in reduced levels of PYD and DPD. Soy isoflavones may have a beneficial effect on bone formation markers, but this requires extensive multi-center research.