Procollagen Type I N Propeptide Research Articles

Bone Turnover Markers After Standard and Distal Roux-en-Y Gastric Bypass: Results from a Randomized Controlled Trial.

Roux-en-Y gastric bypass is associated with increased risk of bone fractures. Malabsorptive procedures may be associated with secondary hyperparathyroidism and detrimental effects on bone health. We aimed to compare the effects of standard and distal gastric bypass on bone turnover markers 2years after surgery. Patients with body mass index (BMI) 50-60kg/m2 (n = 113) were randomized to standard or distal gastric bypass, 105 patients (95%) completed 2-year follow-up. Serum C-terminal telopeptide of type I collagen (CTX-1), procollagen type I N-propeptide (PINP), and bone-derived alkaline phosphatase (BALP) was measured at baseline and up to 2years after surgery. ANCOVA and linear mixed models were used to compare groups. The levels of bone turnover markers increased significantly in both groups, with no statistically significant difference between groups. Two years after standard and distal gastric bypass mean (SD) CTX-1 were 0.81 (0.32) and 0.83 (0.31) μg/L (p = 0.38), mean PINP was 77.6 (23.2) and 77.7 (29.3) μg/L (p = 0.42), and BALP 47.9 (21.9) vs. 50.7 (19.6) μg/L (p = 0.38), respectively. Multiple linear regression analyses showed that PINP and BALP correlated positively (p = 0.01 and p < 0.001) with PTH, but only BALP was significantly higher in patients with secondary hyperparathyroidism (p = 0.001). Type of surgery, vitamin D serum concentrations, and 2-year BMI were all independently associated with PTH levels. A comparable increase in bone turnover markers 2years after standard and distal gastric bypass was observed. There was a higher prevalence of secondary hyperparathyroidism after distal gastric bypass, but this did not impact bone turnover markers. Clinical Trials.gov number NCT00821197.

Influence of Apelin-13 on osteoporosis in Type-2 diabetes mellitus: A clinical study

Objective:To investigate the relationship between serum level of Apelin-13 and bone mineral density (BMD) as well as other parameters, and determine the influence of Apelin-13 on osteoporosis in patients with Type-2 diabetes mellitus.Methods:Seventy-six patients with Type-2 diabetes mellitus were recruited from Department of Endocrinology of our hospital between January 2013 and July2017. The clinical data, including age, gender, height, weight, body mass index (BMI) and disease duration were recorded for all patients. Blood sample was collected for measurement of Apelin-13, Procollagen type-I N propeptide (PINP) and Cross-linked carboxy terminal telopeptide of type-I collagen (ICTP), and BMD was tested with a dual-energy X-ray absorptiometry scanner.Results:The patients were divided into three groups, in which 19 patients were assigned in osteoporosis group, 25 in osteopenia group and 32 in normal group. The level of Apelin-13 in osteoporosis group was significantly lower than that in osteopenia and normal groups (p<0.05), and the value in osteopenia group was significant lower than that in normal group (p<0.05). Correlation analysis showed in the included patients the level of Apelin-13 was positively correlated to the value of BMD and PINP (p<0.05), but negatively correlated to age and ICTP (p<0.05).Conclusion:In conclusion, this study demonstrated that there was a close relationship among Apelin-13, BMD, ICTP and PINP, and Apelin-13 plays an important role in the occurrence of osteoporosis in patients with Type-2 diabetes mellitus.

High dose vitamin D supplementation does not affect biochemical bone markers in multiple sclerosis \u2013 a randomized controlled trial

BackgroundPeople with multiple sclerosis have high risk of osteoporosis and fractures. A poor vitamin D status is a risk factor for MS, and vitamin D supplementation has been recommended both to prevent MS progression and to maintain bone health.MethodsWe assessed the effect of 20,000 IU vitamin D3 weekly compared to placebo on biochemical markers of bone metabolism in 68 persons with relapsing remitting multiple sclerosis.ResultsSerum levels of 25-hydroxyvitamin D more than doubled in the vitamin D group, and parathyroid hormone decreased in the vitamin D group compared to the placebo group at week 48 and week 96. There was however no effect on bone formation as measured by procollagen type I N propeptide (PINP), or on bone resorption as measured by C-terminal cross-linking telopeptide of type I collagen (CTX1). Neither PINP nor CTX1 predicted bone loss from baseline to week 96.ConclusionsThese findings corroborate the previously reported lack of effect of weekly high dose vitamin D supplementation on bone mass density in the same patients, and suggest that such vitamin D supplementation does not prevent bone loss in persons with MS who are not vitamin D deficient.Trial registrationThe trial was registered at ClinicalTrials.gov on April 4 2008, registration number NCT00785473.

Effects of vitamin D combined with pioglitazone hydrochloride on bone mineral density and bone metabolism in Type 2 diabetic nephropathy.

The study aims to investigate the effect of vitamin D (VD) combined with pioglitazone hydrochloride (PIO) on bone mineral density (BMD) and bone metabolism in patients with Type 2 diabetic nephropathy (T2DN). T2DN patients were selected and assigned into mild, moderate, and severe groups. In each group, three therapy regimens (VD, PIO, and VD plus PIO) were administered. X-ray absorptiometry was used to measure BMD. Intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D3 (25-OH-VD3) were measured by chemiluminescence meter. ELISA was applied to detect levels of osteoprotegerin (OPG), bone gla protein (BGP), C-terminal telopeptides of type I collagen (β-CTX), procollagen type I N-propeptide (PINP), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Compared with the mild group, T2DN patients in the moderate and severe groups had longer course of disease and higher levels of total cholesterol (TC), triglyceride (TG), serum phosphorus, fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc) and creatine (Cr), and lower blood calcium. The BMD in different parts increased among the mild, moderate, and severe groups, and the highest BMD was found after VD plus PIO treatment. OPG, iPTH, BGP, β-CTX, Pyr/Cr, and D-Pyr/Cr levels were reduced, while 25-OH-VD3 and PINP levels were elevated among three groups after different treatments, and the most obvious change was observed after VD plus PIO treatment. Our findings indicate that VD combined with PIO may be more effective in improving BMD and bone metabolism than VD or PIO alone in the treatment of T2DN patients, especially for T2DN patients with mild disease.

The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α levels in rheumatoid arthritis.

BackgroundDopamine receptor 2 (DR2) expressions on B cells from Rheumatoid arthritis (RA) patients has been found to be negatively correlated with disease activity and can potentially predict the response to treatment. This study aimed to investigate the role of B cell DR2 expression on bone remodeling in RA.MethodsPatients with RA (n = 14) or osteoarthritis (OA; n = 12), and healthy controls (n = 12) were recruited for this study. Dopamine receptor (DR) 2 expression was assessed using flow cytometry. Pro-inflammatory cytokines, including interleuin(IL)-1β, IL-6, IL-17, and tumor necrosis factor(TNF)-α, and bone turnovers, including osteocalcin (OC),serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (β-CTX), collagen type I cross-linked telopeptide (ICTP), as well as matrix metalloproteinase-3 (MMP-3) and osteoprotegerin (OPG) were measured by electrochemiluminescence, chemiluminescence, or enzyme-linked immunosorbent assay. DR2 expression on synovial B cells from 4 RA patients and 3 OA patients was detected by immunofluorescence.ResultsThere were more DR2+CD19+ B cells in synovial tissues from RA patients than in those from OA patients. The frequency of peripheral B cells that expressed DR2 was positively correlated with plasma TNF-α level. Levels of ICTP and MMP-3 were significantly higher, and OPG were lower in RA patients compared to those in the OA group and healthy controls (all P < 0.05).ConclusionThe frequency of B cells that expressed DR2 showed a correlation with levels of the pro-inflammatory cytokine TNF-α. DR2+CD19+ B cells in synovial tissues might have a role in bone metabolism and TNF-α production.

Effect of age and sex on bone markers in Chlorocebus aethiops raised in captivity.

The objective was to evaluate the procollagen type I N-propeptide (PINP), osteocalcin (OC), β-crosslaps (β-CTX), and parathyroid hormone (PTH) in relation to age and sex of Chlorocebus aethiops in captivity. Seventy-three monkeys were divided into four age groups: AG1 (juvenile); AG2 (young adult); AG3 (adult); and AG4 (senile). An electrochemiluminescence immunoassay with an Elecsys 2010 analyzer was used to determine the serum markers of bone. Sex did not influence the results of the markers. However, the variables PINP, OC, and β-CTX were negatively correlated with age (r = -0.643; r = -0.711; r = -0.488; P < 0.001, respectively), and PTH was correlated positively with age (r = 0.418, P < 0.001). The data obtained can be used as biomarkers of bone metabolism reference intervals in healthy C. aethiops in captivity.

Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population

While epidemiologic studies suggest that bone turnover biomarkers may predict hip fracture risk, findings are inconsistent and Asian data are lacking. We conducted a matched case–control (1:1) study nested in the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women (45–74years) recruited from 1993 to 1998 in Singapore. One hundred cases with incident hip fracture and 100 individually matched controls were randomly selected from 63,257 participants. Serum bone turnover biomarkers, namely bone alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), N-terminal and C-terminal crosslinking telopeptide of type I collagen (NTX-I and CTX-I) were measured using immunoassays. Hip fracture cases had significantly higher serum levels of OC, PINP, CTX-I and NTX-I than controls (p<0.05). There was a dose-dependent positive relationship between OC, PINP, CTX-I and NTX-I and risk of hip fracture (all Ps for trend≤0.006), where the risk was significantly increased by 4.32–8.23 folds for the respective BTM [Quartile (Q) 4 vs. Q1]. The odds ratio [OR (95% CI)] at the highest quartile (Q4) was 6.63 (2.02–21.18) for PINP and 4.92 (1.67–14.51) for CTX-I. The joint effect of PINP and CTX-I showed a 7-fold increase in risk (OR: 7.36; 95% CI: 2.53–21.41) comparing participants with higher levels of PINP (Q4) and CTX-I (Q3–Q4) to those with low levels of PINP (Q1–Q3) and CTX-I (Q1–Q2). Our data demonstrated that higher serum levels of bone turnover biomarkers were associated with increased risk of hip fracture in an Asian population.

Anti-tumor Necrosis Factor Therapy Increased Spine and Femoral Neck Bone Mineral Density of Patients with Active Ankylosing Spondylitis with Low Bone Mineral Density.

To evaluate the effect of anti-tumor necrosis factor (TNF) therapy on bone mineral density (BMD) in patients with active ankylosing spondylitis (AS) with low BMD. Eighty-nine patients with active AS with low BMD were randomly divided into either a study group or a control group. The study group received etanercept (50 mg/week) or adalimumab (40 mg/2 week) subcutaneously for 1 year. BMD of lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry, and bone turnover markers serum C telopeptide of type-I collagen (sCTX) and serum procollagen type-I N propeptide (PINP) were detected by ELISA at baseline and at end of study. After 1 year, compared with baseline, there was a significant increase in spine and femoral neck BMD by a mean ± SD of 14.9% ± 15.6% (p < 0.0001) and 4.7% ± 7.9% (p < 0.0001) in the study group. In the control group, there was a significant decrease in spine and femoral neck BMD by a mean ± SD of -8.6% ± 9.7% (p < 0.0001) and -9.8% ± 11.5% (p < 0.0001). Compared with baseline, sCTX was significantly decreased in the study group (-40% at 1 yr, p < 0.0001), but bone-specific alkaline phosphatase and PINP increased (45.6%, p < 0.0001 and 30.8%, p < 0.0001, respectively). In patients with active AS with low BMD, the spine and femoral neck BMD increased after anti-TNF therapy for 1 year, and it was accompanied by a significant decrease in bone resorption markers and an increase in bone formation markers.

Increased intake of selected vegetables, herbs and fruit may reduce bone turnover in post-menopausal women.

Increased consumption of vegetables/herbs/fruit may reduce bone turnover and urinary calcium loss in post-menopausal women because of increased intake of polyphenols and potassium, but comparative human studies are lacking. The main aim was to compare bone turnover markers and urinary calcium excretion in two randomised groups (n = 50) of healthy post-menopausal women consuming ≥9 servings of different vegetables/herbs/fruit combinations (three months). Group A emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised specific vegetables/herbs/fruit with bone resorption-inhibiting properties (Scarborough Fair Diet), with both diets controlled for potential renal acid load (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12 weeks. Procollagen type I N propeptide (PINP) decreased (−3.2 μg/L, p < 0.01) in the B group only, as did C-terminal telopeptide of type I collagen (CTX) (−0.065 μg/L, p < 0.01) in women with osteopenia compared to those with normal bone mineral density (BMD) within this group. Intervention Groups A and B had decreased PRAL, increased urine pH and significantly decreased urinary calcium loss. Urinary potassium increased in all groups, reflecting a dietary change. In conclusion, Group B demonstrated positive changes in both turnover markers and calcium conservation.

Viabilidade da mensuração de marcadores de remodelação óssea em mulheres com lúpus eritematoso sistêmico

ObjectiveTo investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. MethodsThe study included 43 female SLE patients. Serum procollagen type I N propeptide (PINP), C‐terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti‐cardiolipin, anti‐dsDNA, and anti‐nucleosome levels were measured. ResultsPINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ = 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ = 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under‐45 or over‐45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. ConclusionsIncreased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment.

Changes in serum RANKL and OPG with sexual development and their associations with bone turnover and bone mineral density in a cohort of girls

ObjectivesTo characterize the variations of serum osteoprotegerin (OPG) and RANK ligand (RANKL) with sexual development in adolescent girls, and to estimate their associations with bone turnover and bone mineral density (BMD). Design and methodsWe studied 300 girls evaluated at 13 and 17years of age. Fasting blood samples were collected and the following substances were quantified: RANKL, OPG, C-terminal telopeptide of type I collagen (CTX), and procollagen type I N propeptide (PINP). BMD was measured at the distal forearm. Correlation coefficients were used to quantify associations between those variables at 13 and 17years of age. Random-effects linear models were used to quantify associations between bone parameters and sexual development (years from menarche). ResultsRANKL was positively correlated with bone resorption (CTX) in early and late adolescence (r13=0.15 and r17=0.23) and the OPG/RANKL ratio correlated inversely with CTX at 17 (r17=−0.24). No significant associations were found between RANKL and OPG and bone formation (PINP). In early adolescence, there was an inverse correlation of BMD with CTX (r13=−0.52) but no significant correlations were found between osteoclast regulators and BMD. We observed a linear decrease in serum RANKL with increasing sexual development (−0.09pmol/L per year, 95% CI: −0.10, −0.07) alongside an increase in OPG (0.02pmol/L, 95% CI: 0.01, 0.04). ConclusionsSerum RANKL and OPG levels varied markedly with sexual development in adolescence. These cytokines were not predictive of bone turnover or BMD at 13, but serum RANKL bioactivity was associated with bone resorption in late adolescence.

PINP as a biological response marker during teriparatide treatment for osteoporosis

Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis.

Low-dose hydrocortisone replacement therapy is associated with improved bone remodelling balance in hypopituitary male patients

Glucocorticoid (GC) therapy is associated with adverse effects on bone metabolism, yet the effects of different GC physiological replacement regimens in hypopituitarism are not well characterised. We aimed to assess the effect of three hydrocortisone (HC) replacement dose regimens on bone turnover. An open cross-over study randomising ten hypopituitary men with severe acth deficiency to three commonly used HC dose regimens: dose A (20 mg mane and 10 mg tarde), dose B (10 mg mane and 10 mg tarde) and dose C (10 mg mane and 5 mg tarde). Following 6 weeks of each regimen, the participants underwent 24-h serum cortisol sampling and measurement of bone turnover markers: bone-specific alkaline phosphatase, procollagen type I N-propeptide (PINP), intact osteocalcin (OC(1-49)), C-terminal cross-linking telopeptide (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b). Bone remodelling balance was estimated as an absolute ratio (PINP:CTX-I) and as an index using standardised scores derived from the matched controls. There were significant increases in the concentrations of the formation markers PINP (P=0.045) and OC(1-49) (P=0.006) and in the PINP:CTX-I ratio (P=0.015), and a more positive bone remodelling balance index (P=0.03) was observed in patients on the lowest dose C than in those on the highest dose A. Mean 24-h cortisol concentrations correlated negatively with CTX-I (r=-0.66 and P=0.04) and TRACP5b (r=-0.74 and P=0.01) in patients on dose B and with OC(1-49) (r=-0.66 and P=0.04) and CTX-I (r=-0.81 and P<0.01) in patients on dose C. In patients receiving the lower-dose regimen, trough cortisol concentrations correlated with increased bone formation and resorption. Low-dose HC replacement (10 mg mane and 5 mg tarde) is associated with increased bone formation and a positive bone remodelling balance. This may have a long-term beneficial effect on bone health.

Periarticular Bone Gain at Proximal Interphalangeal Joints and Changes in Bone Turnover Markers in Response to Tumor Necrosis Factor Inhibitors in Rheumatoid and Psoriatic Arthritis

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are characterized by periarticular bone erosion; periarticular bone formation is a feature in PsA. The effect of anti-tumor necrosis factor-α (TNF-α) on periarticular bone remodeling is unclear in both diseases. Our aim was to assess the response of bone turnover markers (BTM) and hand bone mineral density (BMD) to anti-TNF over 3 years in RA and PsA. We measured serum bone-specific alkaline phosphatase (bone ALP), procollagen type-I N-propeptide (PINP), intact osteocalcin, C-terminal cross-linking telopeptides (CTX-I), urinary N-terminal cross-linking telopeptide of type-I collagen (NTX-I), and free deoxypyridinoline crosslinks (fDPD) at baseline, 1, 12, and 36 months. BMD measurements (hands/spine/hip) were obtained at 3 timepoints. We recruited 62 patients (RA 35; PsA 27). BTM correlated significantly with hand BMD but not with central BMD. Low hand BMD was associated with RA and increased BTM. Following anti-TNF therapy, hip BMD declined while spine and hand BMD were unchanged. Periarticular BMD at proximal interphalangeal (PIP) joints increased while it decreased at metacarpophalangeal joints. Bone ALP increased steadily and was always higher in PsA. PINP and intact osteocalcin increased to a lesser extent, but resorption markers did not change. At baseline, hand BMD was inversely associated with BTM. Bone formation rather than resorption markers better showed the bone response to anti-TNF. Despite a lack of effect on central BMD, the modest effect of anti-TNF on PIP BMD may provide evidence that BTM reflect specifically bone remodeling activity at periarticular sites of inflammation in RA and PsA.

Effect of simulated microgravity on osteocytes responding to fluid shear stress

Osteocytes, as most abundant cells and major mechanical sensor in bone, play an important role in the mechanism of microgravity-induced bone loss. The response of osteocytes to fluid flow stress under simulated microgravity was investigated in this study. MLO-Y4, an osteocyte-like cell line, was cultured under simulated microgravity condition for 5 days. Then cells were sheared at 15dyn/cm2 in flow chamber. After 15min shear, nitric oxide (NO) was examined by Griess Reagent and prostaglandin E2 (PGE2) by ELISA. After 6h shear, alkaline phosphatase (ALP) was examined by PNPP, osteocalcin (OC) and procollagen type I N propeptide (PINP) by ELISA. Cells were divided into four groups: CON (1G with no shear), CON-S (1G with shear), SM (simulated microgravity with no shear) and SM-S (simulated microgravity with shear). The results showed that (1) NO, ALP activity, OC and PINP increased significantly while PGE2 showed no change in SM compared with CON. (2) NO, PGE2, ALP activity and PINP increased significantly while OC decreased significantly in CON-S compared with CON. (3) NO in SM-S had no significant difference compared to SM, PGE2 and OC increased while ALP activity and PINP decreased significantly in SM-S compared with SM. (4) The increasing amplitude of PGE2 and OC, the decreasing amplitude of ALP activity in SM-S to SM was lower than that in CON-S to CON. In addition, some changes of F-actin cytoskeleton were observed by confocal microscopy. All results indicated that the response induced by fluid shear in osteocytes could be inhibited by simulated microgravity, namely the mechanosensibility of osteocytes decreased under simulated microgravity. This may partly contribute to the mechanism of microgravity-induced osteoporosis and will be helpful to find out effective description.

Consistency of Bone Turnover Marker and Calcium Responses to Parathyroid Hormone (1–84) Therapy in Postmenopausal Osteoporosis

We investigated whether those who experience the greatest increases in bone turnover in response to parathyroid hormone (PTH) therapy are the same as those who experience elevations in calcium levels. Baseline and follow-up procollagen type I N propeptide (PINP), bone-specific alkaline phosphatase (BAP), C-terminal telopeptide (CTX), and serum and urinary calcium levels were analyzed post hoc from the 119 postmenopausal women with osteoporosis randomized to PTH(1–84) in the Parathyroid Hormone and Alendronate trial. Short-term changes in the markers of bone turnover were highly correlated with one another ( r = 0.57–0.87, p < 0.001). In contrast, change in serum calcium correlated only modestly with changes in markers of formation ( r = 0.22–0.30, p ≤ 0.02) and did not correlate significantly with change in CTX ( r = 0.13, p = 0.18). Participants who experienced hypercalcemia experienced greater 3-mo changes in BAP than those who did not (78% vs. 42% increase in BAP, p = 0.04), with similar trends for PINP and CTX. In conclusion, the use of 1 marker of bone turnover, rather than multiple markers, may be sufficient to assess biochemical response to PTH(1–84). The relationship between bone turnover marker and calcium responses to PTH(1–84) is modest and does not suggest a profound, broadly heightened responsiveness of certain individuals to therapy.

Procollagen type I N-propeptide is a predictor of skeletal morbidity in patients with malignant osteolytic bone disease on bisphosphonates

There is an urgent need for individualized treatment of malignant bone disease (MBD), as the clinical benefit from bone-targeted therapies is moderate. We assessed the predictive value of the bone formation marker procollagen type I N-propeptide (PINP) for skeletal morbidity in patients with MBD receiving pamidronate. Seventy patients with advanced MBD were randomized to receive pamidronate 60 mg (n = 35) or 90 mg (n = 35) every 3 weeks for six cycles in a double-blind study. PINP was analyzed at baseline and before each administration of pamidronate, using a validated ELISA. Serum PINP concentrations were compared with pain response (visual analog scale VAS, composite pain score) and skeletal morbidity (skeletal-related events, SRE) using Student's T-test, Wilcoxon rank-sum and log-rank test, respectively. Patients with ≥20% pain reduction in the VAS had lower baseline PINP concentrations when compared to patients with <20% VAS response (P < 0.0001). A high baseline serum PINP concentration (highest tertile versus lower two tertiles) was significantly associated with a shorter duration of pain response (P < 0.0001) and a shorter time interval to first SRE (P < 0.008). Sensitivity of a low baseline PINP serum concentration for freedom from SRE at 1 year from randomization was 75% (15 out of 20 patients), while specificity was 82% (27 out of 33 patients). Serum PINP has been shown to be a significant predictor for skeletal morbidity in patients with MBD on pamidronate treatment. Prospective validation of PINP in patients with MBD to assess the prognosis or individualize bone-targeted treatment is justified.

Effects of raloxifene and alendronate on bone turnover as assessed by procollagen type I N-Propeptide (PINP)

Effects of raloxifene and alendronate on bone turnover as assessed by procollagen type I N-Propeptide (PINP)

Efficacy of low doses of pamidronate in osteopenic patients administered in the early post-renal transplant

This study evaluates the efficacy of low doses of pamidronate after renal transplantation to prevent bone loss in osteopenic patients. Results show that pamidronate is safe and significantly reduced spinal bone loss when administered immediately after renal transplantation. The purpose of this work is to evaluate the efficacy of two intravenous infusions of pamidronate in the immediate post-transplant period in a renal transplant (RT) population. In this 12-month, randomized, double-blind, multicenter trial, 39 kidney recipients with diagnosed osteopenia received two doses of 30mg of disodium pamidronate (n = 24) or placebo (n = 15), at surgery and 3months post-RT. All patients received calcium and vitamin D. Bone density of the lumbar spine and total femur was measured by dual-energy X-ray absorptiometry (DXA) and X-rays were performed at RT, 6 and 12months post-RT. Biochemical and hormonal determinations were performed before and after treatment. Pamidronate significantly reduced spinal bone loss, but no significant benefit was found for the incidence of fractures. Elevated baseline intact parathyroid hormone (iPTH) and bone remodeling markers returned to normal levels 3months post-RT. However, normal procollagen type I N propeptide (PINP) concentrations were only maintained in the pamidronate group. After RT, a comparable graft function was observed in both groups according to creatinine values, 25-hydroxyvitamin-D (25-OH-D) levels were improved, and serum calcium levels normalized after a transient fall during the first 3months. A low dose of pamidronate prevents bone loss in osteopenic patients when administered immediately after RT.

The effect of a fortified milk drink on vitamin D status and bone turnover in post-menopausal women from South East Asia

Calcium and vitamin D are essential for bone growth; milk is an appropriate vehicle to be fortified with calcium, vitamin D and other minerals. The purpose of the current study was to compare the effect of supplementing with a high calcium milk drink with added vitamin D, magnesium and zinc (HCM) versus a placebo drink on serum parathyroid hormone (PTH) and vitamin D status as well as markers of bone formation/resorption in postmenopausal women living in South East Asia (Jakarta, Indonesia and Manila, the Philippines) over a period of 4 months. Calcium intake at baseline was 237 mg (median; 176–316, interquartile range) for Indonesia and 353 mg (median; 222–480, interquartile range) for the Filipino women per day. Fortified milk supplementation reduced the percentage of women that were insufficient in 25 (OH) vitamin D3 (<50 nmol/L) from 70% to 22% in the Indonesian women and 20% to 0% in the Filipino women. Fortified milk supplementation significantly reduced parathyroid hormone levels (PTH) by week 2 (22% and 11%), C-telopeptide of type I collagen (CTX) by week 2 (34% and 27%), osteocalcin (OC) by week 8 (18% and 25%) and procollagen type I N-propeptide (PINP) by week 8 (15% and 21%), in women from Indonesia and the Philippines, respectively. Thus, the HCM intervention was able to significantly improve vitamin D status, lower PTH levels and reduce bone turnover in two groups of South East Asian women.