Bone Markers In Patients Research Articles

Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression

BackgroundPatients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression.MethodsA total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26).ResultsLinear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009).ConclusionsOur results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males.Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn

Effect of High-Dose Glucocorticoids on Markers of Inflammation and Bone Metabolism in Patients with Primary Glomerular Disease

Background: Glucocorticoids are one of the most commonly used drugs for treatment of inflammatory and autoimmune diseases. Sirtuin-1 (SIRT-1) belongs to the family of proteins involved in protection against inflammation and oxidative stress. A role of SIRT-1 in regulation of bone metabolism during high-dose steroid therapy is unknown. Objectives: The study assessed influence of high doses of intravenous corticosteroids on plasma inflammation and bone markers in patients with primary glomerular disease. Methods: The study included 40 patients (25 M, 15 F; mean age 53.1 ± 14 years) with chronic kidney disease (mean estimated glomerular filtration rate, 58.9 ± 31.3 mL/min). The main inclusion criterion was clinical and histopathological diagnosis of primary glomerular disease and urine protein excretion >2.0 g/24 h. The patients received intravenous pulses of methylprednisolone 20–30 mg/kg/day for three consecutive days followed by oral prednisone 0.8–1.0 mg/kg/day. The blood was taken before administration of methylprednisolone to assess plasma SIRT-1, sclerostin, calcium, phosphate, and parathormone; and first-morning urine sample was taken for measurement of calcium, phosphate, and albumin to creatinine ratio. The same laboratory tests were repeated after 4, 7, and 30 days during steroid therapy. Results: Plasma SIRT-1 increased significantly during steroid administration. Plasma sclerostin did not change significantly. There was a significant linear negative correlation between changes in SIRT-1 levels and sclerostin throughout the study. In a multiple regression model, changes of plasma sclerostin induced by steroid therapy explained the largest part of variance of respective changes of plasma SIRT-1. Conclusions: Plasma SIRT-1 increase during high-dose corticosteroid therapy is negatively related to the change of plasma sclerostin that may suggest a protective role of SIRT-1 against the negative effects of steroid therapy on bone.

The Effect of Recombinant Human TSH on Sclerostin and Other Selected Bone Markers in Patients after Total Thyroidectomy for Differentiated Thyroid Cancer.

The direct effect of TSH on bone metabolism in vivo is difficult to capture as the changes of its concentrations are followed by respective alterations of thyroid hormone levels. We evaluated the effect of recombinant human TSH (rhTSH) on sclerostin and other bone markers in 29 patients after total thyroidectomy for differentiated thyroid cancer (DTC), without any signs of disease recurrence, who received L-thyroxine, most at non-suppressive doses. For two consecutive days, the patients were administered a standard dose of 0.9 mg rhTSH, i.m. Concentrations of sclerostin, osteocalcin, β-CrossLaps, PTH, and some other parameters, were measured before and five days after the first rhTSH administration. The greater the increase in TSH concentration (∆TSH), the greater the decrease in: ∆sclerostin (r = −0.672; p < 0.001), ∆β-CrossLaps (r = −0.580; p < 0.001) and ∆osteocalcin (r = −0.405; p = 0.029) levels, were recorded. The degree of TSH increase depended on the baseline PTH (r = 0.651; p < 0.001), age, and creatinine concentrations. rhTSH strongly inhibited bone turnover, thus, TSH—independently of thyroid hormones—exerted a direct protective effect on bone metabolism. Baseline PTH affected the magnitude of TSH increase and the degree of lowering in sclerostin and β-CrossLaps that suggest factors affecting PTH may play a role in the effect of TSH on the bone.

Prediction of Fracture Risk From Early-Stage Bone Markers in Patients With Osteoporosis Treated With Once-Yearly Administered Zoledronic Acid.

The prevention of fractures is the ultimate goal of osteoporosis treatments. To achieve this objective, developing a method to predict fracture risk in the early stage of osteoporosis treatment would be clinically useful. This study aimed to develop a mathematical model quantifying the long‐term fracture risk after 2 annual doses of 5 mg of once‐yearly administered zoledronic acid or placebo based on the short‐term measurement of bone turnover markers or bone mineral density (BMD). The data used in this analysis were obtained from a randomized, placebo‐controlled, double‐blind, 2‐year study of zoledronic acid that included 656 patients with primary osteoporosis. Two‐year individual bone resorption marker (tartrate‐resistant acid phosphatase 5b [TRACP‐5b]) and lumbar spine (L2‐L4) BMD profiles were simulated using baseline values and short‐term measurements (at 3 months for TRACP‐5b and 6 months for BMD) according to the pharmacodynamic model. A new parametric time‐to‐event model was developed to describe the risk of clinical fractures. Fracture risk was estimated using TRACP‐5b or BMD and the number of baseline vertebral fractures. As a result, the fracture risk during the 2 years was successfully predicted using TRACP‐5b or BMD. The 90% prediction intervals well covered the observed fracture profiles in both models. Therefore, TRACP‐5b or BMD is useful to predict the fracture risk of patients with osteoporosis, and TRACP‐5b would be more useful because it is an earlier marker. Importantly, the developed model allows clinicians to inform patients of their predicted response at the initial stage of zoledronic acid treatment.

Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism

ContextPrimary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis.Patients and methodsWe assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment.Study designObservational longitudinal cohort study.SettingTertiary care hospital.ResultsCompared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers.ConclusionThis study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.

Functional capacity, bone mineral density and neoformation-resorption bone markers in patients under 18 years of age with reduced mobility.

Prolonged immobilization associated with several neurological disorders causes se condary osteoporosis with pathological fractures and persistent bone pain. To establish the association between bone mineral density (BMD), neoformation and bone resorption markers and the degree of functional capacity in children under 18 years of age with reduced mobility. Pa tients and Method: Cross-sectional study conducted in Ciudad Real, Spain between January 1, 2016, and December 31, 2017 with patients aged between 6 and 18 years diagnosed with different neuro logical disorders. The following variables were analyzed: age, sex, pubertal stage, functional capacity according to the Functional Mobility Scale (FMS), which assesses the ability to walk from 5, 50 to 500 meters, BMD, 25-hydroxy-vitamin D, alkaline phosphatase and osteocalcin in blood, and N-terminal telopeptide crosslinks in collagen type I (NTX-I) in urine. BMD, alkaline phosphatase, osteocalcin, and NTX-I values are expressed in Z score according to reference values for age and sex. The Pear son and Spearman correlations were used for data analysis. 36 patients (52.7% girls) with an average age of 8.6±4.7 years. Mean FMS value: 5.3 out of 18. Mean BMD: -1.99 ± 1.7 standard deviations (SD), mean alkaline phosphatase: -2.64 ± 1.08, mean osteocalcin: -2.15 ± 1.39, and mean NTX-I: +3 ± 1.72. There was a significant association between BMD and FMS for 5 meters (r = 0.395; p = 0.017) and for total score (r = 0.365; p = 0.029). There were no significant differences according to the stages of pubertal development. In this population, there was a decrease in BMD and bone neoformation markers, and an increase of bone resorption markers with no association with pubertal development. Patients with a lower degree of mobility present a lower BMD.

The frequency of vitamin D deficiency in chronic kidney disease and its relation with baseline mineral bone markers.

To assess the frequency of Vitamin D deficiency in chronic kidney disease and its association with baseline mineral bone markers in patients visiting nephrology clinics. The observational study was conducted at the Indus Hospital, Karachi, from January 2017 to January 2018, and comprised patients of either gender aged >16 years diagnosed with chronic kidney disease stage I-V. The patients were divided into two groups on the basis of severity of vitamin D deficiency. Severe vitamin D deficiency was defined as <10ng/ml, and moderate deficiency ad 10- 25ng/ml. Data was analysed using SPSS 21. Of the 267 patients, 146(54.7%) were males and 189(70.8%) had vitamin D deficiency. Vitamin D-deficient patients were younger than those with normal levels (p=0.044). Serum creatinine was raised in the deficient patients compared to those with normal vitamin D level (p=0.042). Females and currently employed patients were at a higher risk of having vitamin D deficiency (p=0.048, 0.009). There was no si gn ific ant as s ociation between disease stage a nd vitamin D defic ienc y ( p= 0.311). Vitamin D deficiency was found in a significant proportion of chronic kidney disease patients irrespective of the disease stage. Females, currently employed and young patients were more prone to having vitamin D deficiency.

Alterations of bone metabolism of patients with primary and platinum-sensitive recurrent tuboovarian carcinoma induced by platinum-based chemotherapy with and without bevacizumab

Objective: During the last two decades, survival rates of patients with tuboovarian carcinoma (TOC) have markedly improved, now highlighting the importance of late sequelae of antineoplastic treatment. Direct effects of chemotherapy on the bone metabolism of TOC patients are only poorly elucidated so far. The present translational project sought to gain detailed information on the influence of platinum-based chemotherapy with or without bevacizumab (Bev) on the expression of various bone markers in patients with primary or platinum-sensitive recurrent TOC.

Trabecular Bone Score, Bone Mineral Density and Bone Markers in Patients with Primary Hyperparathyroidism 2 Years After Parathyroidectomy.

Following a parathyroidectomy there is a bone mineral density (BMD) improvement in patients with primary hyperparathyroidism. However, data of bone microarchitecture are scarce. Trabecular bone score (TBS) estimates bone microarchitecture and could provide valuable information in those patients. The aim of this study is to assess TBS changes 2 years after successful surgery in a group of patients with primary hyperparathyroidism and correlate these results with changes in BMD and bone turnover markers. This is a prospective study including 32 patients. In all participants BMD and TBS were measured, before and 24 months after surgery. Biochemical data: serum calcium, PTH, 25-OH-vitamin D, beta-crosslaps, bone alkaline phosphatase, and osteocalcin. 25 female and 7 male patients, mean age 64.6±12.4 years, were included in the study. At baseline, BMD was low at: lumbar spine (T-score -2.19±1.31), total hip (-1.33±1.12), femoral neck (-1.75±0.84), and distal one-third radius (-2.74±1.68). Baseline TBS showed partially degraded microarchitecture (1.180±0.130). After parathyroidectomy lumbar spine BMD increased significantly (5.3±13.0%, p<0.05), as well as total hip (3.8±8.8%, p<0.05). There was an increase in TBS, but this was not significant. There was a correlation between TBS and BAP at baseline (rs=0.73; p<0.01) and TBS and BAP 2 years after surgery (rs=0.57, p<0.05). Although bone density improves 2 years after surgery in patients with primary hyperparathyroidism and there is a restoration of bone turnover markers, TBS is not completely restored. These results remark the necessity of longer periods of study, to confirm if bone microarchitecture could be completely restored after surgery.

Effect of Androgen Deprivation Therapy on Bone Mineral Density in a Prostate Cancer Cohort in New Zealand: A Pilot Study.

Introduction:Reduction in bone mineral density (BMD) is a common side effect of androgen deprivation therapy (ADT). We aimed to examine the cross-sectional and longitudinal variation in BMD and associated bone markers in patients with nonmetastatic prostate cancer (PCa) managed with and without ADT.Methods:Bone mineral density of the total body, lumbar spine, femoral neck, ultradistal forearm, and one-third distal radius was measured in 88 patients with PCa without bone metastases at baseline and at 6 months. Patients were categorized into 4 groups: (1) acute ADT (≤6 months), (2) chronic ADT (>6 months), (3) former ADT, and (4) no ADT (controls). Serum levels of bone metabolism markers, procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX), were also measured.Results:In the cross-sectional analysis, men receiving chronic ADT had significantly lower total body BMD as compared with former ADT users and men with no ADT. In longitudinal analysis, a significant reduction in ultradistal forearm BMD was observed in both acute and chronic ADT users after 6 months (4.08% and 2.7%, P = .012 and .026, respectively). A significant reduction in total body BMD was observed in acute ADT users (2.99%, P = .032). Former ADT users had a significant increase in both lumbar spine and femoral neck BMD (2.84% and 1.59%, P = .008 and .002, respectively). The changes in BMD were not significantly different between acute and chronic ADT users. In the cross-sectional analysis, higher levels of PINP and CTX were observed in acute and chronic ADT users than former ADT users or PCa controls. In longitudinal analysis, the level of serum PINP and CTX did not change significantly from baseline to 6 months in acute, chronic, and former ADT users, or PCa controls, and the percentage change did not differ among the 4 groups.Conclusions:Men on acute ADT had a similar rate of bone loss to men on chronic ADT. Reversibility in ADT-induced bone loss was observed in those who discontinued ADT. Serum levels of PINP and CTX were higher in acute and chronic ADT users and levels returned to the range of PCa controls when treatment was withdrawn.

CLA Has a Useful Effect on Bone Markers in Patients with Rheumatoid Arthritis.

There was no significant difference between the groups in enzyme activity of ALK-P of bone, PGE2 and MMP3 variables. However, differences between the two groups in terms of activity of telopeptides C, Osteocalcin, and IGF1 were significant (P<0.05). CLA has a potentially beneficial effect on bone markers in patients with rheumatoid arthritis. Therefore, in order to study the effect of CLA on bone health in patients with RA and all patients with autoimmune and bone diseases more studies with longer duration and evaluation of bone mass density are required.

No association between vitamin D deficiency and parathyroid hormone, bone density and bone turnover in a large cohort of HIV-infected men on tenofovir.

IntroductionCombination antiretroviral therapy (cART) may affect vitamin D [25(OH)D], parathyroid hormone (PTH), bone mineral density (BMD) and bone turnover (BT). Reduced BMD and secondary hyperparathyroidism have been reported with tenofovir (TDF). We investigated the associations between TDF and bone markers, especially in 25(OH)D-deficient patients.Materials and MethodsIn a single-centre longitudinal study investigating BMD in HIV-positive men, serum 25(OH)D, calcium, phosphate, PTH and alkaline phosphatase (ALP) were measured. Lumbar spine, non-dominant total hip and non-dominant femoral neck BMD (g/cm2) were measured using dual-energy X-ray absorptiometry. BT was assessed by serum type 1 procollagen (P1NP) and carboxy-terminal collagen cross-links (CTX). Mann–Whitney U tests compared serum markers and BT, and t-tests compared BMD according to TDF in all and 25(OH)D-deficient patients.ResultsA total of 422 men were recruited: mean age 47 (SD 9.8) years, 94% white ethnicity, 93% MSM, diagnosed HIV positive for median 9.6 (IQR 5.0,15.5) years, median CD4 547 (IQR 411,696) cells/µL, HIV RNA <40 copies/mL in 87% (96% of those on cART). 25(OH)D (nmol/L) was normal (>75), insufficient (50–75), deficient (25–50) and severely deficient (<25) in 14%, 29%, 50% and 7%, respectively. Of 381 men on cART, 77% were currently on TDF. TDF was not associated with median calcium (p=0.69) or phosphate (p=0.52), but patients had higher (but normal) median ALP [81 (IQR 69,103) vs. 73 (IQR 60,89) IU/L, p=0.005) compared to non-TDF cART. There was no difference in the association between vitamin D and PTH according to whether someone currently was (r=0.11, p=0.06, Figure 1) or was not using TDF (r=0.12, p=0.29, Figure 1). TDF was also not associated with PTH, BMD or BT in either all patients on cART (Table 1a) or in patients with 25(OH)D deficiency (Table 1b). ConclusionsIn this largely TDF-experienced cohort of HIV-positive men, there was no association between TDF and 25(OH)D deficiency, hyperparathyroidism, reduced BMD or increased BT, although patients on TDF had higher but normal ALP. We found no evidence to support additional monitoring of bone markers in patients on TDF regardless of 25(OH)D status.

Prognostic Value of Bone Markers in Patients with Carcinoma

Background: We investigated the usefulness of bone markers, respectively Alkaline Phosphatase (AP) and Tartrat Resistant Acid Phosphatase 5b (TRACP 5b) for diagnosis, treatment and monitoring of patients with carcinoma of different origin. AP is a marker of bone formation, while TRACP 5b is a marker of bone resorption. The isoform 5b of the enzyme TRACP is expressed by osteoclasts and can be measured in blood. Objectives: The aim of this study was to evaluate the prognostic value of the bone markers AP and TRACP 5b to detect bone metastasis and pathological bone metabolism. Materials and Methods: Our study comprised 101 patients with positive tumor markers. Sera of these patients were collected and the bone markers AP and TRACP 5b were determind. TRACP 5b was measured by a colorimetric test which determines the TRACP 5b by using the phophatase activity of this enzyme by dephosphorylation of p-Nitrophenylphosphate (pNPP). The test is a two site immunoassay by Medac Diagnostika, Germany. Results: The sensitivity of AP in our study to detect bone metastasis is 52.9%, the specificity is 53.9%. TRACP 5b shows a sensitivity of 64.7% and a specificity of 70.9%. An elevated TRACP 5b activity is associated significantly with bone metastasis in our study groups (p=0.01). In patients with chronic elevated levels of liver enzymes we could see a significant elevation of TRACP 5b (p=0.005). Conclusion: In conclusion TRACP 5b is more sensitive and specific to detect bone metastasis and bone turnover than the Alkaline Phosphatase. In patients with multimorbidity the origin of AP is not clear due to its multiorganic appearance. The levels of TRACP 5b are elevated in patients with bone metastasis and in patients with chronical dysfunction of the liver. TRACP 5b might be helpful in the diagnostic procedure of tumor-patients to detect bone metastasis. Moreover TRACP 5b seems to be helpful to indicate oncological patients with early dysfunctions in bone metabolism and helps to induce early treatment to these patients.

The influence of ibandronate treatment on bone density and biochemical bone markers in patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is characterized by different signs including increased bone fragility, short stature, blue sclera, abnormal tooth growth and often secondary immobility. No curative therapy has been found for this rare disease up to now, and different pharmacological substances have been tried as treatment for severe forms of OI. Promising results were seen with intravenous bisphosphonates in the treatment of patients with OI. The aim of present study was to show the effect of intravenous ibandronate therapy on bone density and bone metabolism markers. We analyzed the data of 27 patients with the diagnosis of OI who were treated off-label with intravenous ibandronate. Ibandronate was administered by intravenous infusion every three months at a dosage of 0.3–2 mg. Bone turnover markers and bone density were measured before starting therapy and every three months during treatment. Bone density was measured by using an ultrasound imaging system providing an accurate image of the calcaneus and by evaluating broadband ultrasound attenuation (BUA). Twenty-seven patients were treated with intravenous ibandronate during the observation period. 18 were female. The mean age of all patients was 23.9 years ± 19.6 (range 4–63). Seventeen patients were categorized to have OI Type I, 5 patients to have OI Type III and 5 patients to have OI Type IV. There was a statistically significant decrease in total alkaline phosphatase (P<0.0001). We detected also a statistically significant decrease in the ratio urinary deoxypyridinoline/urinary creatinine (P=0.0048) and the ratio urinary pyridinoline/urinary creatinine (P<0.0001) respectively. There was also a statistically significant increase in serum magnesium (P=0.034) and BUA (P=0.0071). No statistically significant changes were seen for total serum calcium (P=0.16), the ratio of urine calcium/urine creatinine (P=0.29), alkaline phosphatase (isoform bone) (P=0.3), procollagen-I-peptide (P=0.5), osteocalcin (P=0.9), serum phosphatase (P=0.71), parathormone (P=0.11) and the ratio urine phosphatase/urine creatinine (P=0.58) Therapy with ibandronate in patients with OI leads to a normalisation of bone turnover markers and increasing bone density. Therefore serum alkaline phosphatase and bone density are possible parameters to monitor bisphosphonate treatment in patients with OI.

The effect of cholecalciferol and ultraviolet radiation B on biochemical bone markers in patients with chronic pancreatitis and fat malabsorption: Results of a randomized, double-blind, clinical trial

The effect of cholecalciferol and ultraviolet radiation B on biochemical bone markers in patients with chronic pancreatitis and fat malabsorption: Results of a randomized, double-blind, clinical trial

The application of bone collagen metabolism markers in bone metastases of breast carcinoma

Objective To evaluate the values of using specific osteolytic bone metabolic markers such as serum type Ⅰ collagen carboxyterminal telopeptide(sICTP),urinary nitrogen-terminal cross-linked telopeptides of type Ⅰ collagen(uNTx),urinary pyridinoline crosslinks(uPYD)in bone metastasis of breast cancer.Methods The levels of slCTP,uNTx and uPYD in 72 patients with breast cancer were measured using ELISA.The sensitivity and specificity of diagnostic value in bone metastasis of breast cancer were cal-culated.Seventy-two patients with breast carcinoma were divided into two groups depending on the presence of bone metastasis according to bone scan findings and confirmed by X-ray and/or CT.The level of bone markers was compared between the two groups.Further relation between bone metabolic marker and tumor behavior in the patients with bone metastases was studied detailedly.Results The levels of all bone mark-ers in patients with bone metastasis were significantly higher than those of in ones without bone metastasis(P＜0.05).A significant correlation was seen between each two markers(r＞0.5,P＜0.01).The sensitivity and specificity was 72.00% and 83.33% in uNTx; 80.56% and 80.56% in uPYD; 80.56% and 97.22% in sICTP,respectively.Evident differences were seen between the extent of skeletal infiltration and the levels of the three biomarkers(P＜0.05).The correlations were seen between the levels of the three biomarkers and the risk of occurrence of bone metastasis(P＜0.05).Conclusion The measurement of sICTP,uNTx and uPYD are of significant utility as biochemical markers of bone metastasis in patients with breast cancer and can be used to achieve a timely diagnosis for bone metastasis of breast cancer. Key words: Breast neoplasms; Bone neoplasms; Neoplasm metastasis; Biological markers; Collagen type Ⅰ

Change in Markers of Bone Metabolism with Chemotherapy for Advanced Prostate Cancer: Interleukin-6 Response Is a Potential Early Indicator of Response to Therapy

Men with androgen-independent prostate cancer (AIPC) frequently have bone metastasis. The effects of chemotherapy on markers of bone metabolism have not been well characterized. We conducted a prospective study of patients with AIPC randomized in the first cycle to receive either docetaxel/estramustine or zoledronic acid, a bisphosphonate, to inhibit osteoclastic activity. Here we report the effects of therapy on markers of bone metabolism in these patients following the first cycle of therapy. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. Changes in markers of bone metabolism were compared in patients receiving initial chemotherapy versus bisphosphonate. There was no significant difference in median change in any of the measured bone markers in patients given zoledronic acid when compared to chemotherapy. When comparing responders to nonresponders, overall interleukin-6 (IL-6) decreased by 35% in prostate-specific antigen responders; whereas, IL-6 levels increased by 76% in nonresponders (p = 0.03). Elevated IL-6 levels and reductions in IL-6 levels early in treatment may reflect ultimate clinical response to docetaxel-based regimens.

Change of bone markers in patients with bone metastases treated with zoledronic acid

Change of bone markers in patients with bone metastases treated with zoledronic acid

A cross-sectional comparison of serum bone markers in patients on stable abacavir (ABC) or tenofovir (TDF) containing therapy

Methods Prospective, cross-sectional, single-centre study of individuals stable for >6 months on ABCor TDF-based regimens (naive to TDF and ABC respectively) and <50 cps/ ml. The study was designed to measure marker of renal and bone function. The serum bone markers were quantified: alkaline phosphatase (ALP; specific and therefore total ALP are useful markers of bone turnover, specifically resorption), beta crosslaps (measure of type I collagen degradation fragments, a marker of osteoclast activity or bone resorption) and osteocalcin (a polypeptide secreted by osteoblasts, a marker of bone formation). Parameters independently, significantly associated with changes in these markers by univariate analysis (p < 0.15) were entered into a multivariable regression model.

Bone mineral density and bone markers in patients with a recent low-energy fracture: effect of 1 y of treatment with calcium and vitamin D

Background: Low-energy fractures of the hip, forearm, shoulder, and spine are known consequences of osteoporosis.Objective: We evaluated the effect of 1 y of treatment with calcium and vitamin D on bone mineral density (BMD) and bone markers in patients with a recent low-energy fracture.Design: In a double-blinded design, patients with fracture of the hip (lower-extremity fracture, or LEF) or upper extremity (UEF) were randomly assigned to receive 3000 mg calcium carbonate + 1400 IU cholecalciferol or placebo (200 IU cholecalciferol). BMD of the hip (HBMD) and lumbar spine (LBMD) were evaluated by dual-energy X-ray absorptiometry, and physical performance was assessed by the timed Up & Go test. Serum concentrations of 25-hydroxycholecalciferol, parathyroid hormone (PTH), telepeptide of type I collagen (ICTP), osteocalcin, and N-terminal propeptide of collagen type I were measured.Results: A total of 122 patients were included (84% women; x̄ ± SD age: 70 ± 11 y); 68% completed the study. In an intention-to-treat analysis, LBMD increased in the intervention group and decreased in the placebo group, and the difference between the groups was significant after 12 mo: 0.931 ± 0.211 compared with 0.848 ± 0.194 (P < 0.05). No significant change was shown for HBMD. The effect of treatment was more pronounced in patients aged <70 y. The intervention decreased bone turnover. PTH was significantly lower in the intervention group (P < 0.01) for the LEF patients. ICTP and change in LBMD were significantly related to physical performance.Conclusions: A 1-y intervention with calcium and vitamin D reduced bone turnover, significantly increased BMD in patients younger than 70 y, and decreased bone loss in older patients. The effect of treatment was related to physical performance.