Indices Of Bone Turnover Research Articles

Yigu decoction regulates plasma miRNA in postmenopausal osteoporosis patients: a randomized controlled trial

BackgroundPostmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD.MethodsIn this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3 months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism.ResultsCompared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P < 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins.ConclusionThis study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner.

7063 Serum Alkaline Phosphatase Level as a Marker for Progressive Central Precocious Puberty

Abstract Disclosure: V.M. Figueredo: None. T. Seeherunvong: None. Background: Precocious puberty is typically associated with a speed up in growth, risk of premature growth plate closure and reduced adult height. Serum alkaline phosphatase (ALP) is a biochemical indicator of bone turnover and studies have shown greater serum ALP levels in pubertal individuals compared to prepubertal controls. We examined serum ALP levels among children with various form of early puberty. We investigated whether serum ALP levels were significantly different between children with premature thelarche or premature adrenarche compared to those with central precocious puberty (CPP). Methods: We conducted a retrospective chart review of patients with early pubertal development attending a pediatric endocrinology clinic between 2017 and 2023. Information on height, weight, serum ALP levels and bone age was obtained. Patients were considered to have CPP based on the results on a GnRH test. Patients with diagnosis of premature adrenarche or premature thelarche were included as controls. This study was approved by Institutional Review Board (IRB). Analysis of data was performed using IBM SPSS Statistics version 29.0.1.0 (171). Results: Among 72 patients included in the study, 22 patients had progressive CPP whereas 50 patients had premature adrenarche or premature thelarche. The prevalence of abnormally elevated serum ALP levels was greater among patients with CPP (22.7%) than among patients with premature adrenarche or premature thelarche (6%). Using logistic binomial regression analysis, serum ALP levels were significantly elevated (p=0.042) in subjects with progressive CPP compared to patients with premature adrenarche or premature thelarche. Both groups had similar BMI values. BMI z-scores and advanced bone age were positively correlated. BMI (p=0.08) and advanced bone age were not significantly different (p=0.12) in the group with CPP compared with the group comprising patients with either premature adrenarche or premature thelarche. Conclusion: These findings suggest that serum ALP levels are helpful as a tool to help distinguish CPP from premature adrenarche or premature thelarche in the evaluation of patients with initial early pubertal development. Presentation: 6/1/2024

Optimization of the Preparation Process and Ameliorative Efficacy in Osteoporotic Rats of Peptide-Calcium Chelates from Skipjack Tuna (Katsuwonus pelamis) Meat.

This study aimed to establish the preparation process of peptide-calcium chelates (TMP-Ca) using skipjack tuna meat and investigate the function and mechanism of TMP-Ca in an osteoporosis model of rats. The results indicated that trypsin is more suitable for preparing the Ca-chelating hydrolysates of tuna meat, and the optimal hydrolysis conditions were derived as follows: digestion time 4 h, material-liquid ratio 1:10, and enzyme dose 3%. The conditions for chelating Ca with tuna meat hydrolysate were optimized to be chelation time 50 min, temperature 50 °C, pH 8.0, and a peptide-Ca ratio 1:10. The prepared hydrolysate was subjected to ultrafiltration, and the fraction (TMP) (MW <1 kDa) showed the highest Ca chelation rate (51.27 ± 1.42%) and was made into the peptide-Ca chelates (TMP-Ca). In osteoporotic rats, TMP-Ca significantly improved the decrease in ovarian indexes caused by retinoic acid. It also elevated serum Ca, phosphorus, and bone turnover indexes, increased the number of bone trabeculae, and improved bone microstructure. In addition, we confirmed that TMP-Ca could regulate the OPG/TRAF6 pathway to reduce osteoclast differentiation, inhibit bone resorption, and promote bone formation. Therefore, TMP-Ca could significantly ameliorate osteoporosis, and this study provides a functional component for the preparation of healthcare products using skipjack tuna meat to treat osteoporosis.

Biochemical Examination of Plasma Ghrelin Levels in Individuals Afflicted With Chronic Periodontal Disease: A Comparative Study.

This study intended to assess plasma ghrelin levels in individuals with chronic periodontitis and analyze potential associations with bone turnover indicators, serum cytokines, and periodontal parameters. The research contained 80 patients each with 40 individuals with periodontally healthy controls (C) (28 males, 12 females) and 40 chronic periodontitis (CP) patients(29 males, 11 females). The blood samples were analyzed for soluble receptor activator nuclear factor kappa B ligand (sRANKL), interleukin-1 beta (IL-1β), total and acylated ghrelin, tumor necrosis factor-alpha (TNF-α), osteocalcin (OSC) and alkaline phosphatase (ALP), and periodontal parameters were recorded. The CP group had considerably higher plasma concentrations of both acylated and total ghrelin than the C group (p<0.05). Gender-based investigation showed substantial differences only among men in both groups (p<0.05). Hence, no significant modifications were identified in serum sRANKL, TNFα, and ALP levels between the groups. However, there was a notable difference in serum OSC and IL-1β levels in the CP group (p<0.05). Furthermore, total ghrelin/acylated ghrelin and total ghrelin/ALP revealed positive correlations. No significant association was found between symptoms and ghrelin levels. The study findings indicate elevated levels of ghrelin and acylated ghrelin in male CP patients.

Effect of Padzahr Tablet on Biochemical Indices of Bone Remodeling in Postmenopausal Females with Osteopenia: A Randomized Double-Blind Placebo-Controlled Trial

Background: Osteoporosis is a complex disease that poses major global public health challenges. Many individuals with osteoporosis turn to complementary and alternative medicine (CAM) for prevention and management. Due to its mineral contents, Padzahr, a type of clay used in traditional Persian medicine, is believed to have bone-forming properties. This study examined the impact of Padzahr on bone remodeling in postmenopausal women with low bone density.Materials and Methods: In this randomized double-blind and placebo-controlled clinical trial, 48 postmenopausal women with osteopenia were included. The participants were divided into two groups, with 24 participants in each group. One group received Padzahr, and the other group received a placebo. The participants took their assigned treatment for 12 weeks. Blood samples were taken from participants at the study’s beginning and end to compare the two groups’ serum levels of bone remodeling biomarkers.Results: At the outset of the study, the two groups were similar and there were no significant differences in any of the measured variables. Additionally, the levels of bone turnover markers were not significantly different between the two groups at the start of the study (P&gt;0.05). After 12 weeks of treatment, the results of the ANCOVA analysis showed no significant changes in the serum levels of bone turnover indices when comparing the Padzahr group to the placebo group (P&gt;0.05). Conclusion: A clinical trial of 3 months of Padzahr treatment in postmenopausal women with osteopenia did not show significant changes in serum markers of bone turnover.

Early bone loss in patients with obstructive sleep apnea: a cross-sectional study

BackgroundObstructive sleep apnea (OSA) and osteoporosis are both prevalent diseases with shared pathophysiological mechanisms and risk factors. However, the association between the two diseases is seldom studied. This study aimed to identify the link between OSA and bone metabolism.MethodsMale participants aged 30–59-years who visited the sleep clinic were continuously recruited. Polysomnography was used to evaluate sleep and respiratory conditions. Blood samples were collected to detect metabolic, inflammatory and bone turnover indicators. High-resolution peripheral quantitative computer tomography was used to measure the non-dominant lateral radius and tibia.ResultsNinety subjects were recruited. The cortical area (Ct.Ar) of tibia of the severe OSA group was significantly higher than that of the mild and moderate OSA groups (P = 0.06 and P = 0.048). There were significant differences between the four groups in terms of total volumetric bone mineral density (vBMD) (F = 2.990, P = 0.035), meta trabecular vBMD (F = 3.696, P = 0.015), trabecular thickness (Tb.Th) (F = 7.060, P = 0.000) and cortical thickness (Ct.Th) (F = 4.959, P = 0.003). The mean values of the OSA groups were lower than control group. Hypopnea index and percentage of total sleep time with SpO2 < 90% were both positively correlated with alkaline phosphatase (R = 0.213, P = 0.044; R = 0.212, P = 0.045). Sleep efficiency was correlated with multiple indicators of the radius.ConclusionsIn non-elderly male populations, OSA patients tended to have lower vBMD, Tb.Th and Ct.Th than non-OSA patients. The negative effect of OSA may mainly affect the osteogenesis process, and is presumed to be related to sleep-related hypoxemia and sleep efficiency.

Gefitinib enhances healing of long bone fractures in rats via inhibition of the epidermal growth factor receptor signal pathway

Purpose: To investigate the influence of gefitinib on healing of long bone fractures in rats, and the involvement of epidermal growth factor receptor (EGFR) signal route in the process.&#x0D; Methods: A model of long bone fracture was established in 30 Sprague-Dawley (SD) rats which were allocated to control and study groups (n = 15/group). Rats in study group received gefitinib (100 mg/kg per day) via gavage, while control rats were given 0.55 % methylcellulose daily for 7 - 42 days. Fracture healing, maximum callus diameter, serum levels of bone markers and mRNA levels of bone turnover indices in the callus, were determined.&#x0D; Results: Following 1 week of therapy, fracture lines were clear in both groups, and callus was produced. On days 7, 14, 21, and 28, maximum callus diameter of study group was significantly higher than that of control group (p &lt; 0.05). However, there was no significant difference in the maximum callus diameter between the two groups after 42 days (p &gt; 0.05). On days 7, 14 and 21, there were significantly higher BALP and PINP levels, and TRACP-5b and CTX values in study group than in control (p &lt; 0.05). On days 7 and 14, study group COLa1 mRNA and osteocalcin (OC) mRNA was significantly raised, relative to control values. On days 7, 14 and 21, COL10 mRNA expression was significantly up-regulated in study group relative to controls (p &lt; 0.05). However, mRNA expression levels of COLa1, OC, COL10, and COL2A1 were similar in both groups at other time points.&#x0D; Conclusion: Gefitinib enhances the healing of long bone fractures and callus formation in rats, probably through inhibition of EGFR signaling pathway. Therefore, gefitinib is beneficial in bone formation in rats.

Bone mineral density and bone turnover markers in osteoarthrosis accompanied by osteodeficiency conditions (review)

Objective: to define bone mineral density and bone turnover indicators in primary osteoarthrosis accompanied with osteodeficiency conditions of varying severity as a means of early osteoarthrosis detection in individuals. Review method. We analyzed 157 Russian and foreign studies of 2005-2022 retrieved from e-Library, Medline, PubMed, PubMed Central, Google Scholar, SpringerLink и Elsevier. The keyword search in Russian and English involved "primary osteoarthritis", "osteoporosis", "osteopenia", "bone mineral density", "markers of bone resorption", "bone formation markers", "bone metabolism regulators", "RANKL/RANK/OPG system". 35 studies were considered the most valuable and eventually reviewed. Conclusion. The analysis suggested that primary osteoarthrosis accompanied by osteodeficiency conditions can be assessed by determining bone mineral density, bone turnover indicators as well as bone turnover regulators.

Evaluation of mineralization balance in patients with hypoparathyroidism

Aims: Surgical complications play a major role in the etiology of hypoparathyroidism. Calcium and phosphorus metabolisms are disrupted by hypoparathyroidism. As a result, bone mineralization is impaired and may cause many pathologies. In clinical practice, parathyroid transplantation is not possible in every patient. In this study, we aimed to evaluate whether it would be possible to prevent the complications caused by hypoparathyroidism with mineral-supplemented medical therapy, even if we could not replace the lost parathyroid tissue. Methods: A total of 79 individuals with hypoparathyroidism (parathormone levels below the reference range for more than one year) secondary to thyroidectomy admitted to our hospital were included in the study. Calcium, phosphorus, alkaline phosphatase (ALP), vitamin D, and creatinine levels were recorded in the last three controls. The relationship between parathormone levels, mineral levels, and ALP, which is an indicator of bone turnover, was analyzed. Results: The mean calcium value was 8.57±0.90 and the mean phosphorus value was 4.46±0.99 in individuals diagnosed as hypoparathyroid with biochemical data. When the relationship between parathormone and the average of the last three calcium values, the relationship between the average phosphorus value, and the relationship between ALP and vitamin D were examined, no significant difference was found (p&lt;0.05). When the relationship between the calcium phosphorus product and its effect on bone mineralization was examined, the mean calcium phosphorus product was 37.64±7.37, and no statistically significant difference was found with parathormone level (p&lt;0.05). Conclusion: Preservation of parathyroid tissue is important for calcium-phosphorus metabolism. Although loss of parathyroid tissue is irreversible, it may be possible to prevent complications with mineral supplementation. As long as calcium and phosphorus balance are maintained externally, bone turnover will be preserved, along with many pathologies caused by hypocalcemia. No matter how low the parathormone level is, the bone mineralization problem caused by hypoparathyroidism can be reduced or even eliminated with mineral levels normalized with medical treatment.

Myocardial Remodeling in Early Chronic Kidney Disease—Mineral and Bone Disorder Model with Low Bone Turnover

Chronic kidney disease—mineral and bone disorder (CKD-MBD) plays a significant role in causing cardiovascular morbidity and mortality related to CKD. CKD-MBD has been studied during advanced stages when changes in inorganic phosphate (Pi) and its hormonal regulation are obvious. The initial phases of myocardial remodeling (MR) in early CKD-MBD remain poorly understood. We induced mild CKD-MBD in spontaneously hypertensive rats using 3/4 nephrectomy. Animals were fed standard chow, containing 0.6% phosphate. In each animal, we analyzed indices of chronic kidney injury, bone turnover and Pi exchange, and assessed the myocardial histology and gene expression profile. Applied CKD-MBD models corresponded to human CKD S1-2 with low bone turnover and without an increase in systemic Pi-regulating factors (parathyroid hormone and fibroblast growth factor 23). In mild CKD-MBD models, we found MR features characterized by cardiomyocyte hypertrophy, interstitial and perivascular fibrosis, intramyocardial artery media thickening, along with alterations in Ppp3ca, Mapk1, Jag1, Hes1, Ptch1, Numb, Lgr4 and Bmp4 genes. Among other genes, the down-regulation of Jag1 was most tightly associated with either myocardial hypertrophy or fibrosis. Myocardial alterations concurrently occurred with mild CKD-MBD and comprised fibrosis preceding cardiomyocyte hypertrophy. The histological features of MR were associated with myocardial P accumulation in settings of low bone turnover, prior to a response of systemic Pi-regulating factors and with alterations in calcineurin, ERK1/2, Notch, BMP and Hedgehog genes.

Comparison of selected prooxidant-antioxidant balance and bone metabolism indicators and BDNF levels between older women with different levels of physical activity

BackgroundGiven a lack of studies precisely indicating how many steps elderly people should take daily for their antioxidant defence, bone metabolism, and cognitive abilities to improve, our study set out to compare the selected antioxidant, prooxidant, bone turnover, and BDNF indicators between elderly women differing in physical activity (PA) measured by the daily number of steps.MethodsThe PA levels of 62 women aged 72.1 ± 5.4 years were assessed based on their daily number of steps and then were used to allocate the participants to three groups: group I (n = 18; <5,000 steps a day); group II (n = 22; from 5,000 to 9,999 steps a day); and group III (n = 22; ≥10,000 steps a day). Blood samples were collected from the participants in early morning hours and subjected to biochemical analysis for prooxidant-antioxidant balance indicators (SOD, CAT, GPx, GR, GSH, UA, MDA and TOS/TOC), bone metabolism indicators (Ca, 25-OH vitamin D, osteocalcin, CTX-I, and PTH), and BDNF levels.ResultsThe groups were not statistically significantly different in the activity of SOD, CAT, GPx, and GR, but their concentrations of GSH (H = 22.10, p < 0.001) and UA (H = 12.20, p = 0.002) proved to be significantly associated with the groups’ daily PA. The between-group differences in the concentrations of MDA and TOS/TOC were not significant, with both these indicators tending to take higher values in group I than in groups II and III. Significant differences between the groups were established for the concentrations of 25-OH vitamin D (H = 24.21, p < 0.001), osteocalcin (H = 7.88, p = 0.019), CTX-I (H = 12.91, p = 0.002), and BDNF (H = 14.47, p = 0.001), but not for Ca and PTH.ConclusionsSignificantly higher concentrations of GSH, slightly lower oxidative stress indicators, significantly higher BDNF levels, and moderately better bone turnover indicators and resorption markers in the group taking more than 5,000 steps a day suggest that this level of PA can promote successful aging. More research is, however, needed to confirm this finding.

Do Clinical Parameters Reflect Local Bone Metabolism in Heterotopic Ossification After Septic or Aseptic THA?

Do Clinical Parameters Reflect Local Bone Metabolism in Heterotopic Ossification After Septic or Aseptic THA?

In Rats, Whole and Refined Grains Decrease Bone Mineral Density and Content through Modulating Osteoprotegerin and Receptor Activator of Nuclear Factor Kappa B.

Wheat is a staple grain in most parts of the world and is also frequently used in livestock feed. The current study looked at the impact of a wheat grain diet on bone turnover markers. Thirty male rats (n = 10) were separated into three groups of ten. The rats in Group 1 were fed a chow diet, while the rats in Group 2 were provided whole grains. The rats in Group 3 were fed refined grains. Each rat's bone mineral content (BMC) and bone mineral density (BMD) were measured after 12 weeks in the tibia of the right hind limb. We also looked at the amounts of bone turnover indicators in the blood. TRAP-5b (Tartrate-resistant acid Phosphatase 5b), NTx (N-telopeptide of type I collagen), DPD (deoxypyridinoline), alkaline phosphatase (ALP), and osteocalcin (OC), as well as the levels of Receptor Activator of Nuclear Factor Kappa B (RANK) and osteoprotegerin (OPG). Rats fed whole and refined grains showed lower BMC and BMD (p < 0.05) than the control group rats. The grain diet resulted in lower OPG, OC, and ALP levels than the chow-fed rats, as well as significantly higher (p < 0.05) levels of RANK, DPD, TRAB 5b, and NTx. In a rat model, an exclusive whole or refined grain diet lowered bone turnover and mass.

Resveratrol Modulates Bone Mineral Density and Bone Mineral Content in A Rat Model of Male Hypogonadism.

To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism. Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed. ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05). Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.

Vitamin D receptor and estrogen receptor gene polymorphisms in men with type 2 diabetes: Effects on Bone Metabolism.

There is an increased fracture risk in type 2 diabetes mellitus [DM] patients independent of bone mineral density [BMD], both in men and women. Estrogen receptor [ER]-alpha and vitamin D receptor [VDR] gene polymorphisms may predispose patients to increased osteoporosis and fracture risk. This study aims to analyze the relationship of the ER-alpha gene and VDR gene polymorphisms with indicators of bone turnover and BMD in male type 2 diabetic patients. Type 2 diabetic men diagnosed with diabetes for at least one year and healthy controls were included in this cross-sectional study. BMD was measured by dual X ray absorptiometry. Gene polymorphisms were evaluated with polymerase chain reaction-restriction length polymorphism. Serum iPTH, calcium, beta-CrossLaps (cTx), osteocalcin, and free testosterone levels were also evaluated. Participants were 141 type 2 diabetic men [55 ± 8 years] and 100 healthy controls [53 ± 7 years]. BMD measurements were not statistically different between the groups. While iPTH [p < 0.05] and serum calcium levels [p = 0.03] were higher in men with type 2 DM; beta-CrossLaps [p = 0.0001], osteocalcin [p = 0.005], and free testosterone [p = 0.04] were lower than controls. The differences in terms of the frequencies of VDR Apa, Taq, Bsm, Fok and ER-alpha polymorphisms were not statistically significant between the groups. No relationship was observed between polymorphisms and BMD in both groups. VDR and ER-alpha gene polymorphisms seem to have no effect on BMD and bone turnover in men with DM.

Rapamycin impairs bone accrual in young adult mice independent of Nrf2.

Advanced age is the strongest risk factor for osteoporosis. The immunomodulator drug rapamycin extends lifespan in numerous experimental model organisms and is being investigated as a potential therapeutic to slow human aging, but little is known about the effects of rapamycin on bone. We evaluated the impact of rapamycin treatment on bone mass, architecture, and indices of bone turnover in healthy adult (16-20weeks old at treatment initiation) female wild-type (ICR) and Nrf2-/- mice, a mouse model of oxidative damage and aging-related disease vulnerability. Rapamycin (4mg/kg bodyweight) was administered by intraperitoneal injection every other day for 12weeks. Mice treated with rapamycin exhibited lower femur bone mineral content, bone mineral density, and bone volume compared to vehicle-treated mice. In midshaft femur diaphysis (cortical bone), rapamycin-treated mice had lower cortical volume and thickness, and in the distal femur metaphysis (cancellous bone), rapamycin-treated mice had higher trabecular spacing and lower connectivity density. Mice treated with rapamycin exhibited lower bone volume, bone volume fraction, and trabecular thickness in the 5th lumbar vertebra. Rapamycin-treated mice had lower levels of bone formation in the distal femur metaphysis compared to vehicle-treated mice which occurred co-incidentally with increased serum CTX-1, a marker of global bone resorption. Rapamycin had no impact on tibia inflammatory cytokine gene expression, and we found no independent effects of Nrf2 knockout on bone, nor did we find any interactions between genotype and treatment. These data show that rapamycin may have a negative impact on the skeleton of adult mice that should not be overlooked in the clinical context of its usage as a therapy to retard aging and reduce the incidence of age-related pathologies.

Spine Bone Texture Assessed by Trabecular Bone Score in Active and Controlled Acromegaly: A Prospective Study.

ContextAcromegalic patients have an increased vertebral fracture (VFx) risk due to bone quality reduction, independently of bone mineral density (BMD).ObjectiveThe aim of the study is to describe bone quality in acromegaly, measured by trabecular bone score (TBS), a noninvasive index for assessing bone microarchitecture.MethodsWe collected data from 18 patients (13 female, age 56.2 ± 15 years) newly diagnosed with acromegaly. Thirty-six age- and sex-matched healthy controls were also recruited. Pituitary function, bone and calcium-phosphorous metabolism, and BMD at spine and femur and TBS (by dual-energy x-ray absorptiometry) were assessed in acromegalic patients at diagnosis and 12 months after the achievement of insulin-like growth factor 1 (IGF-1) normalization.ResultsAt diagnosis, BMD and the VFx prevalence were comparable between patients and controls (28.3 ± 5.9 vs 27.6 ± 3.7 and 11% vs 8.3%), whereas TBS was significantly lower in acromegalic patients (1.20 ± 0.13 vs 1.30 ± 0.06; P < .001) and carboxyterminal telopeptide (CTX) and osteocalcin were significantly higher compared to controls (707 ± 365.7 vs 371 ± 104.1 pg/mL; P = .001 and 31.6 ± 15.4 vs 17.0 ± 5.7 ng/mL; P = .001, respectively). One year after IGF-1 normalization, a significant reduction of bone turnover indexes was observed in the group of acromegalic patients surgically cured (osteocalcin decrease of 61.2%, CTX decrease of 60.3%) compared to the ones controlled by medical therapy (osteocalcin decrease of 39%, CTX decrease of 40.7%; P = .01 and P = .001, respectively). Despite these findings, no TBS or BMD variations were observed.ConclusionAcromegalic patients have impaired bone quality despite normal density. Achieving normal growth hormone secretion rapidly leads to the normalization of bone turnover.

Serum undercarboxylated osteocalcin levels are related to bone disease in hemodialysis and peritoneal dialysis patients

Objectives: In our study, we investigated whether the undercarboxylated osteocalcin (ucOC) is an indicator of bone turnover for patients treated with hemodialysis (HD) or peritoneal dialysis (PD). Furthermore, we have examined the relationships between ucOC levels and other bone inidicators such as osteocalcin (OC), bone specific alkaline phosphatase (B-ALP), calcitonin, vitamin D, intact parathyroid hormone (iPTH), calcium (Ca), phosphate (P), magnesium (Mg) and bone mineral density (BMD). Methods: Study group was consisted of 24 HD, 30 PD patients and 30 control subjects. ucOC measurements were based on precipitation of carboxylated OC with barium sulfate. After precipitation, ucOC was measured in supernatant by ELISA. Results: In chronic kidney disease (CKD), increased ucOC levels were present both in HD and PD groups. The ucOC levels in HD group were higher than those of PD group. ucOC levels in samples after HD were lower than in samples before HD. But there is no difference between groups for ucOC% levels. We observed that ucOC levels for CRF were higher compared to that of control group and statistically significant. ucOC levels were positively correlated with OC, B-ALP, ALP, iPTH, P and Mg levels. There were negative and significant correlations between ucOC levels and BMD values. ucOC has a good discrimination power for both high and low turnover ROD groups. Conclusions: ucOC is a useful marker to evaluation of bone metabolism in patients undergone hemodialysis or peritoneal dialysis in end-stage renal disease.

Skeletal characterization in a patient with Hajdu-Cheney syndrome undergoing total knee arthroplasty

Hajdu-Cheney syndrome (HCS) is a rare genetic connective tissue disorder caused by gain-of-function mutations in the NOTCH2 gene. We report a 38-year-old male HCS patient with a history of multiple pathologic fractures, poor bone stock under intermittent antiresorptive therapy, and secondary osteoarthritis (OA) of the knee, in which we successfully performed total knee arthroplasty (TKA). Next to a detailed skeletal assessment including laboratory bone metabolism markers, dual energy X-ray absorptiometry (DXA), and high-resolution peripheral quantitative computed tomography (HR-pQCT), undecalcified histologic and histomorphometric analysis was performed on intraoperatively obtained tibial cut sections. This multiscale assessment revealed a severe, combined trabecular-cortical microarchitectural deterioration, increased bone turnover indices, and advanced cartilage degeneration, thus demonstrating the crucial role of Notch2 in skeletal and cartilage homeostasis, which is in line with the findings of previous mouse models.

Non-oxidized parathyroid hormone (PTH) measured by current method is not superior to total PTH in assessing bone turnover in chronic kidney disease

Parathyroid hormone (PTH) is a key regulator of bone turnover but can be oxidized invivo, which impairs biological activity. Variable PTH oxidation may account for the rather poor correlation of PTH with indices of bone turnover in chronic kidney disease. Here, we tested whether non-oxidized PTH is superior to total PTH as a marker of bone turnover in 31 patients with kidney failure included from an ongoing prospective observational bone biopsy study and selected to cover the whole spectrum of bone turnover. Receiver Operating Characteristic (ROC) curves, Spearman correlation and regression analysis of non-oxidized PTH, total PTH and bone turnover markers (bone-specific alkaline phosphatase, procollagen N-terminal pro-peptide and tartrate-resistant acid phosphatase 5b) were used to assess the capability of non-oxidized PTH vs. total PTH to discriminate low from non-low and high from non-high bone turnover, as assessed quantitatively by bone histomorphometry. Serum levels of non-oxidized PTH and total PTH were strongly and significantly correlated. Histomorphometric parameters of bone turnover and the circulating bone turnover markers showed similar correlation coefficients with non-oxidized PTH and total PTH. The area under the ROC (AUROC) values for discriminating between low/non-low turnover for non-oxidized PTH and total PTH were significant and comparable (0.82 and 0.79, respectively). For high/non-high turnover the AUROCs were also significant and of the same magnitude (0.76 and 0.80, respectively). Thus, measuring non-oxidized PTH using the currently available method provides no added value compared to total PTH as an indicator of bone turnover in patients with kidney failure.