Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 µg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

Effects of abiraterone acetate plus prednisone on bone turnover markers in chemotherapy-naïve mCRPC patients after ADT failure: A prospective analysis of the italian real-world study ABITUDE.

BACKGROUND: Bone remodeling is disrupted in metastatic disease, which affects > 70% of metastatic castration-resistant prostate cancer (mCRPC) patients. As a result, abnormal levels of specific bone turnover biomarkers (BTMs) are released. In this prospective ancillary analysis of the Italian real-world study ABITUDE, four markers were measured during abiraterone acetate plus prednisone (AAP) treatment in chemotherapy-naïve mCRPC men failing androgen-deprivation therapy. METHODS: Patients were enrolled if a blood sample was obtained before the first administration of abiraterone (baseline); ad-hoc blood samples were withdrawn during routine tests after 3, 6, and 12 months. A centralized lab measured bone alkaline phosphatase (BALP, osteoblast activity marker), type-I collagen-C-telopeptide (CTX-1, bone resorption marker), parathyroid hormone (PTH) and vitamin D (vitD). At each time point, intra-patient variations vs baseline were compared by the signed-rank test (statistical significance: P-value < 0.05). RESULTS: Of 481 patients enrolled in ABITUDE, 186 (median age: 76 [range: 53-93] years) met the substudy criteria: 74.7% had bone metastases, 11.8% were on bone-targeted therapies (BTT) and 14.0% on vitD supplementation. BALP decreased significantly at month 6 (P = 0.0010) and 12 (P < 0.0001) and CTX-1 at month 6 (P = 0.0028); PTH increased at month 3 (P < 0.0001); no significant difference in vitD levels was observed. Similar findings were observed in BTT-untreated patients. The reduction in BALP and CTX-1 levels was more pronounced in patients with than without bone metastases; in the latter group, no significant variation in BALP and CTX-1 levels was observed. CONCLUSIONS: AAP seems to exert an effect on the microenvironment of metastatic but not of normal bone, which likely contributes to its antitumoral activity.

Biochemical Bone Markers During the Transition Period Are Not Influenced by Parenteral Treatment With a High Dose of Cholecalciferol but Can Predict Milk Fever in Dairy Cows.

Despite being studied extensively, there are still many knowledge gaps in milk fever prevention and it is still a prevalent disease. Various interventions have been used in its prevention; however, none has proven to be entirely effective. The study aimed to assess the effectiveness of high dose vitamin D3 parenteral (intramuscularly) administration and the mechanism of its action by studying blood minerals and biochemical bone markers. Further, we assessed the potential of biochemical bone markers, measured in the close-up dry period, as predictors of clinical milk fever after calving. The study was conducted on 56 high yielding, clinically healthy dairy cows, before their 4th or higher lactation. They were divided into three groups based on season (summer and winter) and administration (vitamin D). The winter group was considered as the control group. Cows (n = 13) were parenterally administered a single dose of 10 million IU of vitamin D3 (DUPHAFRAL® D3) ranging between 10 and 2 days before calving (median = 3 days). Each cow was blood sampled once during four sampling period ranges: ~1 month before calving, 10 to 2 days before calving, 12-48 h after calving and 10-20 days after calving. The samples were analyzed for blood minerals, bone specific alkaline phosphatase (bALP) and C-terminal telopeptide of type I collagen (CTx), alkaline phosphatase, and estradiol. Values were compared between samplings and groups. A receiver operating characteristic (ROC) analysis and logistic regression were used to assess the diagnostic accuracy of biochemical bone markers in predicting milk fever. In this study high dose vitamin D3 supplementation did not statistically reduced the incidence of milk fever (milk fever incidences were 15.4, 39.1, and 25% in the vitamin D, winter and summer groups, respectively). A significant effect of vitamin D3 administration on blood minerals or biochemical bone markers was not found at any sampling. We found that the use of biochemical bone markers in the close-up dry period to predict clinical milk fever was applicable only in the winter (housed) group. The area under the curve (AUC) for bALP was 0.804 and 0.846 for CTx using ROC analysis. The bALP curve had the best ratio at the cut-off point 13.85 U/L with 90% sensitivity and 64.3% specificity. While CTx had the ratio of 90% sensitivity and 78.6% specificity at the cut-off point 0.149 ng/mL. Close-up dry dairy cows with CTx ≥0.121 ng/mL had a 3.8 times higher chance of succumbing to milk fever. We were unable to prove that high dose vitamin D3 parenteral administration is a viable technique for milk fever prevention. Biochemical bone markers are a promising tool for predicting milk fever; however, further studies are needed to confirm their clinical use.

Vitamin D, bone alkaline phosphatase and parathyroid hormone in healthy subjects and haemodialysed patients from West Africa: impact of reference ranges and parathyroid hormone generation assays on the KDIGO guidelines.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend targets based on multiples of the upper limit of normal (ULN) of parathyroid hormone (PTH) concentration. However, the ULN has not always been correctly established by manufacturers. While it is known that the ULN is supposed to be higher in African Americans than in Caucasians, it is largely unknown in Africans. METHODS: We established the ULN of PTH concentration in a population of 240 healthy Ivorians using second- and third-generation PTH assays before and after supplementation with 100 000 IU of cholecalferol. We measured the levels of PTH, bone alkaline phosphatase, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in 100 haemodialysed Ivorian patients. RESULTS: The prevalence of vitamin D deficiency in Ivory Coast is low. The ULN obtained using the third-generation PTH assay was similar to that obtained in Caucasians but was higher when PTH was measured using the second-generation PTH assay. According to the KDIGO guidelines, ∼20% of the haemodialysed patients were below twice the ULN and 30% were above nine times the ULN. Approximately 25% of the patients were even >12 times the ULN. We observed a discrepancy in the results between the two PTH assays (14%) that was relatively more important than what we observed from previous studies in Caucasians using the same strategy. CONCLUSIONS: We found a low prevalence of vitamin D deficiency in a tropical country like Ivory Coast. We also established the PTH reference range, which could prove useful for the follow-up of haemodialysed patients, particularly for the large number of patients suffering from secondary hyperparathyroidism who are at high risk of adverse bone events.

Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders.

Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP's with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP's levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.

A Prospective Observational Study on Effect of Short-Term Periodic Steroid Premedication on Bone Metabolism in Gastrointestinal Cancer (ESPRESSO-01).

BACKGROUND: A multicenter prospective observational study evaluated the effect of gastrointestinal cancer chemotherapy with short-term periodic steroid premedication on bone metabolism. PATIENTS AND METHODS: Seventy-four patients undergoing chemotherapy for gastrointestinal cancer were studied. The primary endpoints were changes in bone mineral densities (BMDs) and metabolic bone turnover 16 weeks after initiation of chemotherapy. BMDs, measured by dual-energy x-ray absorptiometry, and serum cross-linked N-telopeptides of type I collagen (sNTX), and bone alkaline phosphatase (sBAP) were assessed for evaluation of bone resorption and formation, respectively. RESULTS: In 74.3% (55/74) of the patients, BMDs were significantly reduced at 16 weeks relative to baseline. The percent changes of BMD were -1.89% (95% confidence interval [CI], -2.67% to -1.11%: p < .0001) in the lumbar spine, -2.24% (95% CI, -3.59% to -0.89%: p = .002) in the total hip, and -2.05% (95% CI, -3.11% to -0.99%: p < .0001) in the femoral neck. Although there was no significant difference in sNTX levels during 16 weeks (p = .136), there was a significant increase in sBAP levels (p = .010). Decreased BMD was significantly linked to number of chemotherapy cycles (p = .02). There were no significant correlations between changes in BMDs and the primary site of malignancy, chemotherapy regimens, total cumulative steroid dose, steroid dose intensity, and additive steroid usage. CONCLUSION: Gastrointestinal cancer chemotherapy with periodic glucocorticoid premedication was associated with reduced BMD and increased sBAP levels, which were linked to number of chemotherapy cycles but independent of primary site, chemotherapy regimen, duration, and additive steroid usage. The Oncologist 2017;22:592-600 IMPLICATIONS FOR PRACTICE: Bone health and the management of treatment-related bone loss are important for cancer care. The present study showed that a significant decrease in bone mineral density (BMD) and an increase in serum bone alkaline phosphatase levels occurred in gastrointestinal cancer patients receiving chemotherapy, which were linked to number of chemotherapy cycles but were independent of primary site, chemotherapy regimen, total steroid dose, and steroid dose intensity. Surprisingly, it seems that the decreasing BMD levels after only 16 weeks of chemotherapy for gastrointestinal cancer were comparable to that of 12-month adjuvant aromatase inhibitor therapy for early-stage breast cancer patients.

Relationship between vitamin D level and related indicators in breastfeeding infants in People's Hospital of Longhua New District in Shenzhen City / 中华临床营养杂志

Objective To investigate the changes of vitamin D level and its relationship with bone alkaline phosphatase(BAP)and parathyroid hormone(PTH)in infants fed with breast milk and vitamin D supplementation for 0-8 months in People`s Hospital of Longhua New District in Shenzhen city.MethodsTotally 67 newborns in the Department of Obstetrics and Gynecology of People`s Hospital of Longhua New District were selected.These newborns were breastfed and began to supplement vitamin D 400 U/d in the 15th day after birth.The serum 25-(OH)D3 and BAP and PTH levels were measured in newborns and 4-/8-month-old infants,and the correlations of serum 25-(OH)D3 with BAP and PTH were analyzed by Pearson correlation analysis.ResultsCompared with the newborns,the serum 25-(OH)D3 [(78.47±36.41)nmol/L,(75.26±34.73)nmol/L],BAP[(231.43±78.81)μg/L,(205.97±71.64)μg/L],PTH[(31.76±11.54)pg/ml,and(32.94±13.82)pg/ml] levels of 4-and 8-month-old infants were significantly higher,and the difference were statistically significant(t4 months=7.823,12.568,11.852,t8 months=7.364,9.473,11.947;all P=0.000).There was a negative correlation between serum 25-(OH)D3 and BAP in newborns and 4-/8-monthold infants(r=-0.372,-0.463,-0.309;P=0.008,0.016,0.021),the serum BAP was positively correlated with PTH in infants aged 4 months and 8 months(r=0.487,0.338;P=0.005,0.032),and the serum 25-(OH)D3 was negatively correlated with PTH in infants aged 4 months(r=-0.297,P=0.041).Conclusions Infants at birth are prone to vitamin D deficiency in Shenzhen City.After 4 months of breastfeeding and vitamin D400U/d supplementation,the vitamin D levels in most infants become normal.25-(OH)D3 is correlated with BAP and PTH in different months.

Effect of zinc supplementation on bone formation in hemodialysis patients with normal or low turnover bone.

Zinc (Zn) is an essential trace element, which has been shown to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption in vitro. In thalassemia, major patients Zn supplementation was reported to increase whole-body bone mineral content and areal bone mineral density. Therefore, we investigated the effect of Zn supplementation on bone formation in hemodialysis (HD) patients. Nine male patients with age of 66 (35-78) years indicated by median (range), HD vintage of 57 (4-97) months and serum intact parathyroid hormone (PTH) of 113 (6-310) pg/mL were supplemented with polaprezinc containing 34 mg Zn/day for 18 months. Doses of vitamin D were not changed during supplementation. Blood was collected at baseline, 3, 6, 12 and 18 months. Serum Zn increased significantly from 58 (52-65) µg/dL to 71 (57-93) µg/dL at three months and remained unchanged until 18 months. No changes were observed in serum intact PTH during supplementation. Although we found no changes in serum bone alkaline phosphatase (BAP) during Zn supplementation analyzed by Friedman test and Scheffe post hoc test, a significant trend of increase in serum BAP was verified by Jonckheere-Terpstra test (p = 0.0409). On the contrary, there was no trend in serum TRACP5b by Jonckheere-Terpstra test. Therefore, we suggested the effect of Zn supplementation on promoting bone formation, not affected by the status of PTH and vitamin D, in HD patients with normal or low turnover bone.

Bone alkaline phosphatase in CKD-mineral bone disorder.

Overall and cardiovascular mortality in patients with chronic kidney disease (CKD) is greatly increased, without obvious current effective treatments. Mineral and bone disorder (MBD) is a common manifestation of CKD and contributes to the high risk of fracture and cardiovascular mortality in these patients. Traditionally, clinical management of CKD-MBD focused on attenuation of secondary hyperparathyroidism due to impaired renal activation of vitamin D and phosphate retention, although recently, adynamic forms of renal bone disease have become more prevalent. Definitive diagnosis was based on histologic (histomorphometric) analysis of bone biopsy material supported by radiologic changes and changes in levels of surrogate laboratory markers. Of these various markers, parathyroid hormone (PTH) has been considered to be the most sensitive and currently is the most frequently used; however, the many pitfalls of measuring PTH in patients with CKD increasingly are appreciated. We propose an alternative or complementary approach using bone alkaline phosphatase (ALP), which is directly related to bone turnover, reflects bone histomorphometry, and predicts outcomes in hemodialysis patients. Here, we consider the overall merits of bone ALP as a marker of bone turnover in adults with CKD-MBD, examine published bone histomorphometric data comparing bone ALP to PTH, and discuss possible pathogenic mechanisms by which bone ALP may be linked to outcomes in patients with CKD.