Tartrate-resistant Acid Phosphatase Type 5b Research Articles

Bone: A Neglected Endocrine Organ?

Bone has traditionally been viewed in the context of its structural contribution to the human body. Foremost providing necessary support for mobility, its roles in supporting calcium homeostasis and blood cell production are often afterthoughts. Recent research has further shed light on the ever-multifaceted role of bone and its importance not only for structure, but also as a complex endocrine organ producing hormones responsible for the autoregulation of bone metabolism. Osteocalcin is one of the most important substances produced in bone tissue. Osteocalcin in circulation increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral adipose tissue. In males, it has also been shown to enhance testosterone production by the testes. Neuropeptide Y is produced by various cell types including osteocytes and osteoblasts, and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. Hormonal disorders are often associated with abnormal levels of bone turnover markers. These include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide) and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). Bone, however, is not exclusively comprised of osseous tissue. Bone marrow adipose tissue, an endocrine organ often compared to visceral adipose tissue, is found between trabecula in the bone cortex. It secretes a diverse range of hormones, lipid species, cytokines, and other factors to exert diverse local and systemic effects.

Thick Skin on the Dorsal Spine in Osteoproliferative Disease: Ossification of the Posterior Longitudinal Ligament and Diffuse Idiopathic Skeletal Hyperostosis.

Background Although the correlation between reduced skin thickness and reduced bone density has been investigated, no study has evaluated skin thickness and osteoproliferative diseases, including ossification of the posterior longitudinal ligament (OPLL) and diffuse idiopathic skeletal hyperostosis (DISH). Methodology This retrospective cohort study consisted of 99 consecutive patients aged ≥60 years treated for spinal surgery at our hospital between January 2022 and March 2023. Skin thickness was measured at the dorsal side of the cervical, thoracic, and lumbar vertebrae on the sagittal cross-section image of whole-spine CT. Based on the median value, skin thickness was categorized into two groups based on a median thickness of 4 mm. Bone mineral density (BMD) was assessed. The sum of the vertebral body and intervertebral bridging osteophytes of the anterior longitudinal and posterior longitudinal ligament were defined as the OALL index and OPLL index. Serum levels of bone metabolism-related markers, such as tartrate-resistant acid phosphatase type 5b, procollagen I N-propeptide, 25-hydroxyvitamin D, and periostin, were measured. To assess the association between skin thickness and imaging findings, we calculated the adjusted odds ratios, adjusting for age, sex, and body mass index (BMI) and using univariate and multivariate logistic regression analyses. Results No significant differences were found in skin thickness in the three dorsal regions of the cervical, thoracic, and lumbar spine (median = 3.3 mm versus 3.5 mm versus 3.4 mm, p = 0.357) and bone metabolism-related markers. Adjusting for age, sex, and BMI, cervical, thoracic, and lumbar skin thicknesses were related to DISH, the OPLL index, and the OPLL and OPLL index, respectively. Conclusions Skin thickness did not correlate with BMD but with the amount of spinal ossification. A correlation was found between skin thickness and vertebral and intervertebral ossification; vertebral osteophytes, OPLL, and DISH may be more common in thicker skin.

Bone Turnover Markers, n-Terminal Propeptide of Type I Procollagen and Tartrate-Resistant Acid Phosphatase Type 5b, for Predicting Castration Resistance in Prostate Cancer.

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan-Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

Identification and Functional Analysis of Tartrate-Resistant Acid Phosphatase Type 5b (TRAP5b) in Oreochromis niloticus.

Tartrate-resistant acid phosphatase type 5 (TRAP5) is an enzyme that is highly expressed in activated macrophages and osteoclasts and plays important biological functions in mammalian immune defense systems. In the study, we investigated the functions of tartrate-resistant acid phosphatase type 5b from Oreochromis niloticus (OnTRAP5b). The OnTRAP5b gene has an open reading frame of 975 bp, which encodes a mature peptide consisting of 302 amino acids with a molecular weight of 33.448 kDa. The OnTRAP5b protein contains a metallophosphatase domain with metal binding and active sites. Phylogenetic analysis revealed that OnTRAP5b is clustered with TRAP5b of teleost fish and shares a high amino acid sequence similarity with other TRAP5b in teleost fish (61.73-98.15%). Tissues expression analysis showed that OnTRAP5b was most abundant in the liver and was also widely expressed in other tissues. Upon challenge with Streptococcus agalactiae and Aeromonas hydrophila in vivo and in vitro, the expression of OnTRAP5b was significantly up-regulated. Additionally, the purified recombinant OnTRAP5b ((r)OnTRAP5) protein exhibited optimal phosphatase activity at pH 5.0 and an ideal temperature of 50 °C. The Vmax, Km, and kcat of purified (r)OnTRAP5b were found to be 0.484 μmol × min-1 × mg-1, 2.112 mM, and 0.27 s-1 with respect to pNPP as a substrate, respectively. Its phosphatase activity was differentially affected by metal ions (K+, Na+, Mg2+, Ca2+, Mn2+, Cu2+, Zn2+, and Fe3+) and inhibitors (sodium tartrate, sodium fluoride, and EDTA). Furthermore, (r)OnTRAP5b was found to promote the expression of inflammatory-related genes in head kidney macrophages and induce reactive oxygen expression and phagocytosis. Moreover, OnTRAP5b overexpression and knockdown had a significant effect on bacterial proliferation in vivo. When taken together, our findings suggest that OnTRAP5b plays a significant role in the immune response against bacterial infection in Nile tilapia.

Bone Turnover Markers: Basic Biology to Clinical Applications.

Bone turnover markers (BTMs) are used widely, in both research and clinical practice. In the last 20 years, much experience has been gained in measurement and interpretation of these markers, which include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide); and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). BTMs are usually measured by enzyme-linked immunosorbent assay or automated immunoassay. Sources contributing to BTM variability include uncontrollable factors (eg, age, gender, ethnicity) and controllable factors, particularly relating to collection conditions (eg, fasting/feeding state, and timing relative to circadian rhythms, menstrual cycling, and exercise). Pregnancy, season, drugs, and recent fracture(s) can also affect BTMs. BTMs correlate with other methods of assessing bone turnover, such as bone biopsies and radiotracer kinetics, and can usefully contribute to diagnosis and management of several diseases such as osteoporosis, osteomalacia, Paget's disease, fibrous dysplasia, hypophosphatasia, primary hyperparathyroidism, and chronic kidney disease-mineral bone disorder.

Protective effect of Spirulina against bone fragility induced by Garcinia cambogia in high-fat diet induced obese rats

The present work evaluated the protective effects of Spirulina against the bone fragility caused by Garcinia cambogia in high-fat diet induced obese rats. High-fat diet and high-fat emulsion (HFD+HFE) were administered via oral gavage to 30 six-week-old female Sprague Dawley rats for six weeks to induce obesity, except for a normal group (n = 6). Following four weeks of treatment, the diet-induced obese groups were orally administered, daily, with (1) G. cambogia (GC); (2) Spirulina (S); and (3) G. cambogia + Spirulina (GC+S). The normal and obese control groups were treated with equal volumes of 0.9% saline water. It was found that GC significantly decreased body mass index (BMI) below the obese range (0.68 g/cm2). Additionally, GC altered bone mineral density (BMD), increased phosphate and calcium levels, and decreased maximum force and mineral apposition rates (MAR) as compared to the obese control group (p &lt; 0.05). Bone fragility caused by GC was confirmed by the decrease in bone formation marker osteocalcin (OCN), as well as an increase in bone resorption receptor activator of nuclear factor kappa-B ligand (RANKL) and tartrate-resistant acid phosphatase type 5b (TRAP5b) as compared to the obese control group. Spirulina also decreased the BMI of the obese rats. Spirulina also increased blood bone markers, BMD, maximum force, and Young’s modulus. Rats supplemented with GC+S demonstrated higher double-labelled surface (dLS/BS) and MAR as compared to those in the GC group (p &lt; 0.05). Meanwhile, the S group demonstrated improvement in all dynamic histomorphometric indices. S and GC+S groups demonstrated bone formation upregulation and bone resorption downregulation, thus indicating a bone protective effect of Spirulina. Overall, GC treatment led to bone fragility. GC+S treatment significantly augmented bone formation and mineralisation in obese rats as compared to the GC treatment alone. Rats in the S group demonstrated effective weight reduction while showing no destructive effects on the bone.

Application of bone metabolic parameters in the diagnosis of growing pains.

ObjectiveThe present study aimed to assess the diagnostic significance of serum bone metabolic parameters in children with growing pains (GPs).MethodsAll patients diagnosed with GP and healthy controls matched with age and gender were recruited at the outpatient clinic of Children's Hospital at Zhejiang University School of Medicine from August 2016 to August 2021. In all subjects, serum levels of calcium (Ca), phosphorus (P), procollagen type‐I N‐terminal (PINP), parathormone (PTH), 25‐hydroxyvitamin D (25‐(OH)D), osteocalcin (OC), N‐terminal cross‐linked telopeptides of type‐I collagen (CTX), and tartrate‐resistant acid phosphatase type 5b (TRACP5b) were investigated. The univariate analysis, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve were used to identify the bone metabolic parameters factors for diagnosing GP.ResultsWe enrolled 386 children with GP and 399 healthy controls in present study. The mean age of GP group was 5.319 years, and, primarily, the subjects were preschool‐age children. The gender ratio (male‐to‐female) was 1.27 in GP group. After adjusting for age and gender, we identified that the serum levels of Ca (p < 0.001, OR: 25.039), P (p = 0.018, OR: 2.681), PINP (p < 0.001, OR: 1.002), and PTH (p = 0.036, OR: 0.988) were independent diagnostic factors associated with GP. Area under curve (AUC) of the ROC curves was in the order: PINP (0.612) > Ca (0.599) > P (0.583) > PTH (0.541). A combination of independent diagnostic factors and multivariable logistic regression analysis provided a refined logistic regression model to improve the diagnostic potential, of which the AUC had reached 0.655.ConclusionsSerum levels of Ca, P, PINP, and PTH could be independent diagnostic factors associated with GP. The logistic model was significantly superior to bone metabolic parameters for diagnosing GP.

Bone Metabolism, Bone Mineral Content, and Density in Elite Late Teen Female Sprinters.

With intensive training, bone injuries are a major concern for athletes. To assess bone condition, we often measure bone turnover markers, bone mineral content and density; however, in junior athletes, it is not easy to distinguish changes caused by bone injuries from those caused by growth, because the metabolism is increased in both cases. Moreover, although some studies have examined female endurance athletes, knowledge regarding changes in static and dynamic bone conditions in late teen athletes is limited. In this study, we measured the bone mineral content and density, as well as bone turnover markers, in 40 elite female sprinters in their late teens. Whole body mode dual-energy X-ray absorptiometry was performed to measure bone mineral content and density. Blood samples were collected to determine bone resorption and formation markers at the end of track season in 2016 and during the same period of the following year. Body weight and bone mineral content significantly increased, and tartrate-resistant acid phosphatase type 5b, bone-type alkaline phosphatase, and osteocalcin significantly decreased after a year. Furthermore, the rate of change in bone mineral content was higher in younger athletes, indicating that bone growth approaches completion in the late teen years and that bone metabolism accordingly decreases.

Comprehensive assessment of tissue and serum parameters of bone metabolism in a series of orthopaedic patients.

Bone diseases represent an increasing health burden worldwide, and basic research remains necessary to better understand the complexity of these pathologies and to improve and expand existing prevention and treatment approaches. In the present study, 216 bone samples from the caput femoris and collum femoris of 108 patients with degenerative or dysplastic coxarthrosis, hip fracture, or osteonecrosis were evaluated for the proportion of trabecular bone (TB) and expression of parathyroid hormone (PTH) type 1 receptor (PTH1R), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Serum levels of PTH, OPG, soluble RANKL (sRANKL), alkaline phosphatase (AP), osteocalcin, total procollagen type-1 intact N-terminal propeptide (TP1NP), tartrate-resistant acid phosphatase type 5b (TRAP5b), sclerostin, and C-telopeptide of type-1 collagen (ICTP) were also determined. Age was positively correlated with serum levels of PTH, OPG, and sclerostin but negatively associated with TB and sRANKL. Women exhibited less TB, lower sclerostin and ICTP, and higher TRAP5b. Impaired kidney function was associated with shorter bone decalcification time, less TB, lower sRANKL, and higher serum PTH, OPG, and sclerostin. Furthermore, correlations were observed between bone PTH1R and OPG expression and between serum PTH, OPG, and AP. There were also positive correlations between serum OPG and TP1NP; serum OPG and sclerostin; serum AP, osteocalcin, and TRAP5b; and serum sclerostin and ICTP. Serum OPG was negatively associated with sRANKL. In summary, clear relationships between specific bone metabolism markers were observed, and distinct influences of age, sex, and kidney function, thus underscoring their suitability as diagnostic or prognostic markers.

Ankle loading ameliorates bone loss from breast cancer-associated bone metastasis.

Breast cancer is a serious health problem that preferentially metastasizes to bone. We have previously shown that bone loss can be prevented by mechanical loading, but the efficacy of ankle loading for metastasis-linked bone loss has not been investigated. This study showed that body weight was decreased after inoculation of tumor cells, but ankle loading restored a rapid weight loss. The nonloading group exhibited a decrease in bone volume/tissue volume (BV/TV), trabecular thickness, and trabecular number (all P < 0.01) as well as an increase in trabecular separation (P < 0.001). However, ankle loading improved those changes (all P < 0.05). Furthermore, although the nonloading group increased the tumor bearing as well as expression of IL-8 and matrix metalloproteinase 9, ankle loading decreased them. Induction of tumor in the bone elevated the osteoclast number (P < 0.05) as well as the levels of nuclear factor of activated T-cells cytoplasmic 1, NF-κB ligand, cathepsin K, and serum tartrate-resistant acid phosphatase type 5b, but ankle loading reduced osteoclast activity and those levels (all P < 0.05). Tumor bearing was positively correlated with the osteoclast number (P < 0.01) and negatively correlated with BV/TV and the osteoblast number (both P < 0.01). Collectively, these findings demonstrate that ankle loading suppresses tumor growth and osteolysis by inhibiting bone resorption and enhancing bone formation.-Yang, S., Liu, H., Zhu, L., Li, X., Liu, D., Song, X., Yokota, H., Zhang, P. Ankle loading ameliorates bone loss from breast cancer-associated bone metastasis.

Congenital Hypothyroidism and Bone Remodeling Cycle.

Objective:The present study aimed to evaluate the biochemical markers of bone turnover in children with congenital hypothyroidism during the course of treatment as compared to healthy children selected as controls.Methods:The study included 31 children with congenital hypothyroidism and 29 healthy children. In both groups, we evaluated serum procollagen type-1 N-terminal propeptide (PINP) and tartrate-resistant acid phosphatase type 5b isoform (TRACP 5b) levels as bone turnover markers.Results:In both groups, thyroid hormone levels were within normal limits. The levels of vitamin D were significantly higher in the cases with congenital hypothyroidism. Although PINP levels were not found to be different, TRACP 5b levels which are related to osteoclastic activities were significantly higher in the control group.Conclusion:We did not detect an increase in bone resorption in patients with congenital hypothyroidism, despite long-term treatment with LT4. Our results suggest that with effective vitamin D treatment and thyroxin replacement, congenital hypothyroidism is not a deleterious factor for bone turnover.

Fetal Bone Formation Is Decreased from Middle Pregnancy to Birth

Fetal bone development is a complex process that is regulated and maintained by minerals, hormones, and growth factors delivered from the mother via the placenta. Various biochemical markers of fetal bone development have been identified. However, many aspects of this process remain unclear. The aim of the study was to measure the activities of serum tartrate-resistant acid phosphatase type 5b (TRACP 5b) as a bone resorption marker and bone alkaline phosphatase (BAP) as a bone formation marker in preterm and term neonates, and to investigate fetal bone development in middle and late pregnancy. The study included 111 neonates (87 preterm and 24 term) born at Dokkyo Medical University Hospital. Neonates with illnesses and maternal diseases were excluded. Serum samples were collected within 3 hours after birth and stored at -80°C. Univariate and multivariate linear regression analyses were performed. The 111 neonates (median birth weight, 1,510 g) were born at a median of 31.3 weeks of gestation, and had TRACP 5b and BAP activities of 10.9 ± 4.0 U/L and 127.5 ± 49.2 U/L, respectively. TRACP 5b activity showed a tendency to be higher in term neonates, while BAP activity tended to be lower in term neonates. Importantly, TRACP 5b activity was positively correlated with gestational age and birth weight, and BAP activity was negatively correlated with gestational age, rate of born small-for-gestational-age neonates, and birth weight. These results suggest that bone formation during fetal growth is gradually decreased from middle pregnancy to birth, whereas bone resorption is gradually increased.

Changes in serum vitamin D and PTH values using denosumab with or without bisphosphonate pre-treatment in osteoporotic patients: a short-term study.

BackgroundDenosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL). Previous reports have shown that denosumab treatment of osteoporotic patients decreases bone resorption and fracture risk, but there have been no clinical studies on changes in bone turnover markers, 1,25(OH)2D3, or parathyroid hormone (PTH) in denosumab therapy with or without bisphosphonate (BP) pre-treatment in Japan.MethodsHere, we report such findings in 22 patients (11 in the denosumab alone group and 11 in the BP pre-treated group) with osteoporosis following 4 months of treatment. Bone metabolism had been inhibited by prior BP administration in the BP pre-treated group.ResultsThe bone resorption markers serum tartrate-resistant acid phosphatase type 5b and urinary type I collagen cross-linked N-telopeptide were significantly decreased from baseline values for the entire study period in both groups. The bone formation marker bone alkaline phosphatase was significantly decreased at 4 months in the denosumab alone group only, and N-terminal propeptide of type 1 procollagen was significantly decreased at 2 and 4 months in the denosumab alone group versus no remarkable change in the BP pre-treated group. In the denosumab alone group, 1,25(OH)2D3 and PTH were significantly increased at 1 week and decreased gradually thereafter, but these did not change notably in the BP pre-treated group.ConclusionsOur results suggest that treatment with denosumab causes a strong inhibitory effect on bone resorption markers and mild inhibitory effect on bone formation markers. 1,25(OH)2D3 and PTH were significantly increased by denosumab but these did not change in the BP pre-treated group.Trial registrationCurrent Controlled Trials NCT02156960. Registered 31 May 2014.

High Bone Turnover Is Present in Patients with Primary Systemic (AL) Amyloidosis and Increased Osteoprotegerin Identifies Patients with Poor Survival within Mayo Stage 1 Disease

Lytic bone involvement in primary systemic (AL) amyloidosis is uncommon. To-date, there is no systematic study of bone metabolism in patients with AL amyloidosis. For this reason, we evaluated prospectively 102 patients with previously untreated AL amyloidosis who were diagnosed between January 2000 and June 2008 in the Plasma Cell Dyscrasias Unit of the Department of Clinical Therapeutics (Athens, Greece). All patients had histologically confirmed AL amyloidosis, while the definition of organ involvement, hematological and organ response and progression were based on consensus criteria. The levels of the following bone remodeling indices were measured before the administration of any kind of therapy: i) osteoclast regulators: soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), osteoprotegerin (OPG), chemokine C-C motif ligand 3 (CCL-3, previously known as MIP-1alpha) and osteopontin; ii) bone resorption markers: C- and N- telopeptide of type-1 collagen (CTX and NTX, respectively) and tartrate resistant acid phosphatase type-5b; iii) bone formation markers: bone-alkaline phosphatase and osteocalcin. The results were compared with those of 35 age- and gender-matched healthy controls, 40 patients with monoclonal gammopathy of undetermined significance (MGUS) and 35 newly diagnosed, untreated patients with symptomatic multiple myeloma (MM).The median age of AL patient was 65 years (range: 39-80 years); 43% were males; 60% had heart involvement, 73% renal involvement, 11% liver involvement and 40% had peripheral/autonomous nerve system involvement; 67% of patients had two or more organs involved; 16% had a baseline serum creatinine >2 mg/dl. The median serum albumin was 3.2 g/dl, the median serum β2-microglobulin was 1.8 mg/L and the median 24h urine protein was 3350 mg/24h. Median NT-proBNP was 1954 pg/ml; 26%, 41% and 33% of patients were Mayo stage -1, -2 and -3, respectively.None of AL patients had lytic bone lesions in plain radiography or other features suggestive of MM, such as hypercalcemia, significant anemia unrelated to renal impairment or predominant Bence-Jones proteinuria. Bone resorption (assessed by CTX or NTX) in AL-patients was increased (p<0.001) compared to healthy controls but bone formation had no difference between AL patients and controls. CCL-3, sRANKL and OPG were increased in AL patients compared to controls (p<0.01 for all comparisons), but the ratio of sRANKL/OPG was similar in AL patients vs. controls (p=0.854). MM patients had increased bone resorption and decreased bone formation markers compared to AL patients, while sRANKL/OPG ratio was markedly decreased in AL vs. MM, due to high levels of OPG in AL vs MM patients (>4 fold higher; p<0.001). Compared to MGUS, AL patients had decreased sRANKL/OPG ratio due to increased OPG. OPG levels correlated with NT-proBNP levels (p<0.001) and were slightly higher in patients with cardiac involvement (p=0.028).Patients with OPG levels above the upper value of healthy controls had a shorter survival (p=0.026), while AL patients with OPG levels in the top quartile had short survival (12 months vs. 58 months, p=0.024). In the multivariate analysis cardiac biomarkers outperformed OPG; however, in patients with Mayo stage-1 disease, OPG levels remained significant and identified patients with short survival within the “favorable risk” group (12 vs. >60 months, p=0.012; see the Figure). Although renal involvement did not affect bone markers, in AL patients with serum creatinine >1.5 mg/dl, CTX and NTX were higher than in patients with <1.5 mg/dl (p<0.001 and p=0.016, respectively). Neither the involvement of other organs nor the number of involved organs appeared to influence bone remodeling in any way.We conclude that elevated bone resorption and high bone turnover is present in AL patients possibly due to direct and indirect activity of amyloid fibrils or light chains in bone cells. Increased OPG in AL is not only a compensation factor to osteoclast activation but it may also reflect tissue damage in the heart. There is published evidence that OPG is produced by cardiac cells and has been associated with poor prognosis in heart disorders, including heart failure and acute coronary disease. In AL amyloidosis, high OPG is able to identify patients at increased risk of death, mainly within the more favorable prognosis group by Mayo staging. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

FRI0289 Comparison of A Tumor Necrosis Factor Inhibitor, an Interleukin-6 Inhibitor, and Conventional Disease-Modifying Anti-Rheumatic Drugs on Bone Quality in Patients with Rheumatoid Arthritis

BackgroundRecently, attention has been focused on bone quality, independent of bone mineral density (BMD), as a risk factor for fractures. Serum and urine pentosidine and serum homocysteine are typical bone-quality...

BIOCHEMICAL MARKERS OF BONE RESORPTION AND HORMONAL REGULATION OF BONE METABOLISM FOLLOWING LIVER TRANSPLANTATION

Aim. Comparative evaluation of two biochemical markers of bone resorption and hormonal regulation of bone metabolism in liver recipients. Methods and results. B о ne densitometry of L2–L4 and neck of femur, serum level of some hormones (PTH, vitamin D 3 , estradiol, testosterone) regulating osteoclastogenesis as well as com- parative analyses of two bone resorption markers β -crosslaps and tartrate-resistant acid phosphatase type 5b (TRAP-5b) were ful fi lled in patients after orthotopic liver transplantation (OLT). In 1 month after OLT bone density reduction of L2–L4 and neck of femur; decrease of vitamin D 3 , estradiol in women, testosterone in men and increase levels of bone resorption markers were observed. In 1 and 2 years after OLT the rise of bone density, increased levels of PTH, estradiol, testosterone and decreased β -crosslaps levels were revealed, while vitamin D 3 and TRAP-5b levels remained stable. Conclusion. TRAP-5b was found to be a more specif fi c marker of bone resorption, independent from collagen metabolism in liver. Osteoporosis de fi ned in long-term period after OLT was associated with higher TRAP-5b and revialed in women with low estradiol level.

BIOCHEMICAL MARKERS OF BONE RESORPTION, REGULATION OF OSTEOCLASTOGENESIS AND BONE LOSS FOLLOWING LIVER TRANSPLANTATION

Methods and results: bone densitometry of L2-L4 and neck of femur, the level in serum of blood some hormones (PTH, vitamin D3, estradiol, testosterone) and cytokines (OPG, IL-6, FNO-a) regulating osteoclastogenesis as well as comparative analyses of two bone resorption markers β-crosslaps and tartrate-resistant acid phosphatase type 5b (TRAP-5b) were fulfilled at different periods following orthotopic liver transplantation. At the early date after operation there were the bone density decrease of L2-L4, the lowering of vitamin D3, estradiol in women, testosterone in men and the elevation of cytokines and of resorption markers. In 1 and 2 years following liver transplantation there were revealed the rise of bone density, the level of PTH, estradiol, testosterone, which were associated with the lowering of IL-6, FNO-a and β-crosslaps while the level of vitamin D3 and TRAP-5b remained stable. Conclusion: at the early date TRAP-5b was more specific marker of bone resorption which did not depend on collagen metabolism in liver. In 1 and 2 years following liver transplantation bone resorbtion was association with level of PTH, FNO-a and OPG.

Bone turnover markers predict changes in bone mineral density after parathyroidectomy in patients with renal hyperparathyroidism

Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT), which causes varying degrees of bone mass loss. This condition is treated with parathyroidectomy (PTX). We investigated whether serial serum bone turnover markers could predict changes in bone mineral density (BMD) after PTX. Renal patients on maintenance haemodialysis who received PTX for refractory SHPT (n = 26, male/female: 13/13; mean age: 48·6 ± 10·7 year) and control subjects without SHPT (n = 25) were prospectively followed for 1 year at two tertiary hospitals in Taiwan. Serum intact parathyroid hormone (iPTH), bone-specific alkaline phosphatase (BAP) and type 5b tartrate-resistant acid phosphatase (TRAP) were measured serially. Additionally, femoral neck (FN) and lumbar spine (LS) BMD were measured before and 1 year after PTX. After PTX, iPTH levels decreased markedly and persistently. BMDs increased in both the FN and LS, but particularly in the LS. Serum BAP progressively increased to a peak at 2 weeks after PTX. Serum TRAP levels progressively decreased over 6 months after PTX. In univariate correlation analyses, baseline iPTH correlated positively with T-score changes in FN (r = 0·45, P = 0·021) and LS (r = 0·48, P = 0·013). In multivariate regression models, changes in FN T-scores were negatively predicted by baseline BAP levels (r = -0·615, P = 0·005) and baseline FN T-scores (r = -0·563, P = 0·012), and they were positively predicted by baseline TRAP(r = 0·6, P = 0·007). Changes in LS T-scores were positively predicted by baseline TRAP values (r = 0·528, P = 0·01) and negatively predicted by the percentage change in BAP after 2 weeks (r = -0·501, P = 0·015). Parathyroidectomy provided marked, sustained improvements in BMD for up to 1 year. Furthermore, markers of bone turnover predicted 1-year changes in FN and LS BMDs after PTX.

Parathyroidectomy leads to decreased blood lead levels in patients with refractory secondary hyperparathyroidism

ObjectiveSecondary hyperparathyroidism (SHPT) is characterized by high bone turnover and may result in increased release of lead (Pb) from bone stores. Parathyroidectomy (PTX) drastically changes bone remodeling. This study investigated the effects of PTX on the levels of blood lead (blood Pb) in patients with refractory SHPT. MethodsThe study included 30 patients on long-term hemodialysis (HD) who underwent PTX in the nephrology units of two Taiwanese hospitals. Changes in serum levels of intact parathyroid hormone (iPTH), bone-specific alkaline phosphatase (BAP), type 5b tartrate-resistant acid phosphatase (TRAP), total calcium (tCa), and blood Pb were analyzed. ResultsAfter PTX, serum iPTH was markedly decreased while serum BAP was progressively increased and peaked 2weeks after PTX. Serum TRAP levels were progressively decreased during the 4week follow-up period. Serum tCa and blood Pb levels decreased sharply immediately after PTX. There was a positive correlation between the percentage of decrease in tCa and blood Pb at one day after PTX. Further analysis indicated a significant positive correlation between levels of blood Pb and serum iPTH (r=0.378, p<0.001), blood Pb and serum TRAP (r=0.180, p<0.05), and a negative correlation between blood Pb and serum BAP (r=−0.205, p<0.05). ConclusionPTX effectively suppressed the elevated levels of blood Pb and serum bone remodeling markers, which are common features of SHPT. In addition to decreased Pb release from bone, an increased store of Pb in bone may play a role in decreasing serum blood Pb levels. These findings suggest that patients undergoing PTX for refractory SHPT should strictly avoid environmental exposure to Pb.

Effect of zoledronic acid on tartrate-resistant acid phosphatase isoform type 5b and other bone markers in lung cancer patients with bone metastases

Correspondence: Goetz H Kloecker James Graham Brown Cancer Center, University of Louisville, 529 S Jackson St, Louisville, KY 40202, USA Tel +1 502 562 4246 Fax +1 502 562 6811 Email ghkloe01@louisville.edu Background: Up to 44% of lung cancer patients eventually develop bone metastases. Zoledronic acid has been shown to prevent skeletal-related complications in these patients. Bone metabolic markers play an important role in the prediction and diagnosis of bone metastasis. Measurement of serum tartrate-resistant acid phosphatase (TRAP) type 5b and other markers of bone formation and resorption might determine the response of bone metastasis to zoledronic acid therapy. Here we report the effect of zoledronic acid on bone metabolic markers in lung cancer patients. Methods: Patients with lung cancer metastatic to bone undergoing monthly treatment with zoledronic acid were enrolled in this study. Serum markers of activity of bone resorption and formation were collected at baseline, during chemotherapy, before and after zoledronic acid treatment, and every 2 weeks for the first 6 weeks, and then monthly for a total of 6 months or earlier, if bone metastases progressed radiologically. Resorption markers included N-terminal telopeptide of type I collagen, TRAP type 5b, C-terminal telopeptide of type I collagen, and deoxypyridinoline. Bone-specific alkaline phosphatase was the only bone formation marker included. The data were analyzed using the linear mixed-effects model and paired t-test. Results: Twenty-eight participants were enrolled. Thirteen patients could not be evaluated because of low-quality samples (n = 7), noncompliance (n = 5), or withdrawal of consent (n = 1). During chemotherapy without zoledronic acid, levels of TRAP type 5b remained stable. Fourteen days after zoledronic acid treatment, mean N-terminal telopeptide of type I collagen, TRAP type 5b, and bone-specific alkaline phosphatase levels decreased by 41.4% (P = 0.003), 44.9% (P = 0.014), and 12.9% (P = 0.031), respectively. These markers remained significantly decreased during monthly zoledronic acid. C-terminal telopeptide of type I collagen and deoxypyridinoline levels did not change with zoledronic acid treatment. Conclusion: TRAP type 5b, N-terminal telopeptide of type I collagen, and bone-specific alkaline phosphatase levels decreased significantly with zoledronic acid treatment in lung cancer patients with bone metastasis. The rapid response of TRAP type 5b levels to bisphosphonate therapy makes it an attractive tool for monitoring the efficacy of bone-targeted therapy in lung cancer patients.