ResearchPad - vitamin-d Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Association between the rs1544410 polymorphism in the vitamin D receptor (VDR) gene and insulin secretion after gestational diabetes mellitus]]> Genetic variants involved in vitamin D metabolism have been associated with diabetes and related syndromes/diseases. We wanted to investigate possible associations of polymorphisms in genes involved in vitamin D metabolism with indices of insulin resistance and insulin secretion, and also with development of diabetes after gestational diabetes mellitus (GDM).Materials and methodsWe have studied 376 women with previous GDM. Eight single nucleotide polymorphisms (SNPs) in the genes for vitamin D receptor (VDR) [rs731236, rs7975232, rs10735810, and rs1544410], vitamin D binding protein (DBP) [rs7041 and rs4588], and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) [rs10877012 and rs4646536] were genotyped by TaqMan Allelic Discrimination Assay using the Quantstudio 7 Flex system. A 75-g oral glucose tolerance test (OGTT) was performed 1–2 years postpartum. The homeostasis model assessment of insulin resistance (HOMA-IR) and the disposition index [(insulinogenic index: I30/G30)/HOMA-IR] were used to calculate insulin resistance and insulin secretion, respectively. Serum samples for determination of 25(OH)D3 were collected at the time of the OGTT. Manifestation of diabetes was followed up to five years postpartum.ResultsAfter adjustment for BMI, age, and ethnicity, the A-allele of the VDR rs1544410 polymorphism was found to be associated with increased disposition index (difference per allele = 3.56, 95% CI: 0.4567–6.674; p = 0.03). The A-allele of the DBP rs7041 polymorphism was found to be associated with 25(OH)D3 levels (difference [in nmol/L] per allele = −5.478, 95% CI: -8.315 to −2.641; p = 0.0002), as was the T-allele of the DBP rs4588 polymorphism (OR = −6.319, 95% CI: −9.466 to −3.171; p = 0.0001). None of the SNPs were significantly associated with HOMA-IR or postpartum diabetes.ConclusionsThis study provides evidence that the rs1544410 polymorphism of the VDR gene may be associated with increased insulin secretion in women after pregnancy complicated by GDM. Further studies in other populations are needed to confirm the results. ]]> <![CDATA[MON-393 Evaluation of Bone Mass in Transgender Women After Gender Affirming Surgery - a Pilot Study]]> Estrogen deficiency is classically associated with bone loss in both men and women. In transgender women, after being submitted to gender-affirming surgery (GAS), the main goal of hormone therapy (HT) is to maintain the female phenotype and prevent the consequences of the orchiectomy-related hypogonadal state. The aim of this study was to evaluate the impact of GAS on bone mass in transgender women. A total of 142 trans women attending the outpatient Gender Identity Program were sequentially enrolled. Patients aged < 20 and > 60 years (n=15), with gluteal silicone prosthesis (n=26) and without FSH dosage after surgery (n=9) were excluded. Anthropometric evaluation, laboratory tests and dual-energy X-ray absorptiometry (DXA) were performed in all patients during the follow-up. In women undergoing CAS (CAS-Y), DXA was performed at least 12 months after surgery and with estrogen therapy. In the other women (CAS-N), tests were performed after at least 3 months of standardized treatment (estradiol plus spironolactone or cyproterone acetate). Patients with testosterone values still above the reference for women were not excluded as long as they were on regular HT. Ninety two trans women were included. Among them, 30 had performed CAS, and had DXA assessment performed 37 months (21-78) after surgery. The mean age and BMI were 37 years (33 - 46) and 24.9 kg/m² (23.1 - 27.5) in patients CAS - Y and 30 years (24 - 36) and 24.3 kg/m² (21.5 - 28.5) in patients CAS - N. Trans women CAS-Y were significantly older (p=0.000). No difference was observed regarding estradiol levels between the groups [105.7pmol/L (48.4-207.8) and 147.5 pmol/L (71.9-284.5), p=0.622]. Free androgen index (FAI) was significantly higher [0.45 (0.17 - 1.63) and 4.47 (0.70 - 36.4), p=0.002] and FSH significantly lower [60.4mIU/ml (37.9 - 75.6) and 2.6mIU/ml (0.6 - 4.4), p=0.000] in trans women CAS - N. BMD (g/cm²) and Z-score of lumbar spine, femoral neck and total femur did not differ significantly between the groups. Considering all participants, the lumbar spine BMD was negatively correlated with FSH levels (r=-0.343, p=0.005), which remained significant even after adjustments for FAI. When only CAS - Y trans women were considered, a negative correlation was found between FSH levels and lumbar spine (r=-0.598, p=0.001) and hip (r=-0.404, p=0.033) BMD. In a multiple regression model adjusted for age and surgery, women with FSH > 35 mIU/ml presented a prevalence rate ratio of 11.79 for low bone mass (p=0.040, IC 95% 1.19 - 124.39). The results of this pilot study in trans women show no difference in bone mass according to GAS status. However, long-term elevated FSH levels observed in some post GAS - trans women, even on HT, presented a negative association with bone mass. Further studies with greater sample sizes are needed to confirm the impact of GAS on bone mass and fracture risk.

<![CDATA[MON-385 Insulin Resistance and Osteoporosis in People Living with HIV]]> The life expectancy of people living with HIV (PLHIV) increased considerably after the advent of antiretroviral therapy (ARV). Nowadays, it is almost the same as the general population. However, this increase in survival exposes PLVH to age-related morbidities, including chronic metabolic and bone diseases. PLHIV has a low bone mineral density (BMD) and a high prevalence of osteoporosis. Moreover, the frequency of diabetes mellitus (DM) seems to be twice the frequency of the general population. Insulin resistance and DM might be associated with bone diseases in PLHIV. Our study aim was to evaluate the association between insulin resistance and osteoporosis in PLHIV. We carried out a cross-sectional study at the municipality of Santa Maria, South Brazil. PLHIV age 50 yrs or over on treatment with ARV were included. All subjects registered to receive ARV in the university hospital during the period 2016 to 2018 were invited to participate. Those who accepted responded to a standardized questionnaire, performed a bone density scan and a lateral spinal X-ray, underwent peripheral blood collection, and had their weight and height measured. Insulin resistance was considered present when HOMA-IR> 2.7 (Gelonese, 2009). The TyG index was also calculated (VASQUES, 2011). Of the 101 PLHIV who agreed to participate, 84 underwent both insulin and BMD measurements. The prevalence of osteoporosis was 19%. Vertebral fractures were twice as frequent in individuals with osteoporosis (73.3% vs. 36.5%, p = 0.018). Participants with osteoporosis had lower BMI and triglyceride values than those without it. The frequency of insulin resistance calculated by HOMA-IR was 68.2%, and it was associated with glucocorticoid use, smoking, and BMI. HOMA-IR [4.8(6.6) vs. 8.68(9.6), p =0.013], and TyG [5.0(0.3) vs. 5.2 (0.4), p=0.029] mean values were lower in the group with osteoporosis; however, this association disappeared after correction for BMI in the logistic regression model. In conclusion, in our study, PLHIV with osteoporosis have lower insulin resistance than PLHIV without it. Nevertheless, this finding appears to be relating to a lower BMI. Further studies are needed to assess the effect of insulin resistance on fracture risk in PLVH.

GELONEZE, B. et al. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS). Arq Bras Endocrinol Metabol. 2009 Mar;53(2):281-7

VASQUES, A. C. et al. Análise Crítica do Uso dos Índices do Homeostasis Model Assessment (HOMA) na Avaliação da Resistência à Insulina e Capacidade Funcional das Células-C Pancreáticas. Arq. Bras. Endocrinol. Metab., 2008;52/1:32-39.

<![CDATA[OR13-02 Treatment with Zoledronic Acid Subsequent to Denosumab Cannot Fully Prevent Bone Loss]]> Purpose: Treatment with denosumab (DMAB) decreases bone resorption and fracture risk. Following discontinuation, bone resorption increases, bone mass is lost and fractures have been reported. The aim of the study was to investigate if an infusion of zoledronic acid (ZOL) can prevent increases in bone turnover and bone loss in patients previously treated with DMAB and if the timing of the ZOL infusion is important. Methods: The study was a 2-year randomized, open label, interventional study in patients with osteopenia after DMAB treatment for an average of 4.6 years. ZOL was administrated 6 months (6M group, n=20) or 9 months (9M group, n=20) after the last DMAB injection or when bone turnover was increased (OBS group, n=20). Patients in the OBS and the 9M groups were monitored closely and if p-carboxy-terminal collagen crosslinks (CTX) increased > 1.26 ug/l (50% above the range for postmenopausal women and elderly men), if BMD decreased > 5% at the lumbar spine or total hip, or if a patient suffered a low energy vertebral or hip fracture, ZOL was administered. In the OBS group, ZOL was administered no later than month 6. The patients were monitored with DXA 6, 12 and 24 months after treatment. ZOL was re-administered if BMD decreased > 5% at the lumbar spine or total hip or if CTX increased above 1.26 ug/l. We report the outcome 12 months after the initial ZOL infusion. The study is ongoing. Results: A total of 60 postmenopausal women and men with a mean age of 67.7 (range 51-85) years were enrolled in the study. In the OBS group 1, 2, 6, 1 and 0 patients fulfilled the CTX or BMD criteria for treatment 1, 2, 3, 4 and 5 months after baseline. The remaining 10 patients were treated at month 6. In the 9M group 2 patients fulfilled the CTX criteria for ZOL treatment at month 2. A total of 10, 5 and 5 patients in the 6M, 9M and OBS groups, respectively were re-retreated. In the 6M group CTX decreased initially, but increased rapidly thereafter, and 6 months after ZOL, CTX was 0.60±0.08 g/L (mean±SEM). CTX increased rapidly in the 9M and OBS Groups before ZOL, was suppressed by ZOL but increased again thereafter; CTX was 0.47±0.05 μg/L and 0.47±0.05 μg/L 6 months after ZOL in the 9M and the OBS groups, respectively. Mean CTX was within the premenopausal reference range 12 months after ZOL in all 3 groups. From study baseline to twelve months after ZOL BMD at the lumbar spine had decreased by 4.8±0.7%, 4.1±1.1%, and 4.7±1.2% in the 6M, 9M and OBS groups, respectively (p≤0.002 for all without differences between groups) and at the total hip by 2.6±0.5%, 3.2±0.8%, and 3.6±0.8% in the 6M, 9M and OBS groups, respectively (p≤0.001 for all without differences between groups). The decline in BMD was more pronounced in the months before ZOL in the 9M and OBS groups whereas the decline was steadier in the 6M group. Conclusion: Treatment with ZOL irrespective of the timing did not fully prevent loss of BMD in patients with osteopenia.

<![CDATA[MON-397 Potential Relationship Between Hypothyroidism and Bone Loss at Dental Implants]]> Introduction: Hypothyroidism (HT) is an endocrine condition with autoimmune and inflammatory etiologies. Studies have shown that both periodontal disease and peri-implant bone loss are bidirectionally influenced by systemic inflammatory conditions, such as diabetes, adverse pregnancy outcomes, cardiovascular disease, and osteoporosis.1 There also is evidence that HT is associated with decreased bone metabolism, depressed bone turnover, and a prolonged bone remodeling cycle.2 Consequently, the objective of this study was to determine if the severity of bone loss around dental implants is related to the presence of HT.

Methods: Following IRB approval, medical, dental, and radiographic records of patients who received dental implant placement at a university-based postgraduate program in periodontics from 2000–2017 were reviewed (1480 implants; 635 patients). Rate of bone loss in mm/year was calculated from surgical implant placement and subsequent re-evaluation radiographs, with correction for radiographic distortion. Presence of HT was confirmed by review of patient medical records, clinical diagnosis of HT, and history of thyroid hormone supplementation. Populations were adjusted for smoking, diabetes, use of systemic steroids, presence of autoimmune disease (other than HT), and systemic inflammatory conditions. Calculations were performed using IBM SPSS Statistics v25.

Results: Patients with HT had a decreased rate of crestal alveolar bone loss around dental implants. Specifically, patients with HT experienced peri-implant bone loss at a rate of 0.42 mm/year, while bone loss from patients without HT was 1.34 mm/year (68.7% decrease; mean difference = 0.92 mm/year, 95% confidence interval = 0.39–1.50 mm/year, P<0.002). There were no significant differences in patient oral hygiene, or in implant service time, among any of the groups studied (P>0.05).

Conclusions: The results suggest that the rate of marginal alveolar bone loss at dental implants is significantly decreased in patients with HT, and occurs independently of any of the systemic conditions noted above. The findings imply that potential changes in bone metabolism and remodeling associated with HT might result in less peri-implant alveolar bone loss following implant placement surgery. As a result, there does not appear to be an increased risk of peri-implant crestal bone loss in patients with HT.

References: 1Kim J., Amar S., Odontol. 94(1):10–21, 2006. 2Tuchendler D., and Bolanowski M.,Thyroid Res. 7:12, 2014.

<![CDATA[OR13-01 Comparison of Vitamin D Metabolism in Deficient and Sufficient States]]> Objective: to study the differences in calcium-phosphorus and vitamin D metabolism in healthy individuals with deficient and sufficient baseline state of vitamin D. Materials and methods: The study included 16 young conditionally healthy individuals, divided into two equal groups: with levels of 25(OH)D below and above 30 ng/ml determined by the immunochemiluminescent method (Group A and Group B respectively; DEQAS certified). All participants were evaluated for the biochemical parameters of blood and urine, characterizing calcium-phosphorus metabolism, PTH by commercial methods, and vitamin D metabolites (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3 and 24,25(OH)2D3) by HPLC/MS-MS before oral intake of 150 000 IU of an aqueous solution of cholecalciferol and 7 days after administration. Results: At baseline, the level of vitamin D metabolite 25(OH)D2 in Group B was lower with no significant differences in other studied parameters. In group A, strong positive correlations were observed between levels 25(OH)D3 and 3-epi-25(OH)D3, 24,25(OH)2D3, while in group B there were no such associations. After taking a loading dose of cholecalciferol, the groups showed generally similar changes in the studied vitamin D metabolites: a statistically significant increase in 25(OH)D3, 3-epi-25(OH)D3, a decrease in 25(OH)D2, and a ratio of 24,25(OH)2D3 to 25(OH)D3. However, the level of 24,25(OH)2D3 did not change in group B, with a significant increase in group A. The medians of the studied biochemical parameters in blood/urine, as well as PTH, remained unchanged in both groups. Conclusion: In patients with inadequate baseline levels of 25(OH)D, after a loading dose of cholecalciferol, there is a tendency to formation of more inactive forms of vitamin D. These deviations in the metabolism of vitamin D need to be clarified, since they can potentially affect the effectiveness of cholecalciferol therapy.

<![CDATA[OR13-07 Crystal Bone: Personalized, Short-Term Fracture Risk Prediction with Natural Language Processing Methods]]> Fragility fractures due to osteoporosis are common and are associated with significant clinical, personal, and economic burden. Even after a fragility fracture, osteoporosis remains widely underdiagnosed and undertreated. Common fracture risk assessment tools, such as FRAX1 and Garvan,2 confer risk over the long term but do not provide short-term risk estimates necessary to identify very high-risk patients likely to fracture in the next 1–2 years. Furthermore, these tools utilize cross-sectional data representing a subset of all available clinical risk factors for risk prediction. Thus, these methods are generalized across patient populations and may not fully utilize patient histories commonly found in electronic health records (EHRs) that contain temporal information for thousands of unique features. The Optum® de-identified EHR dataset (2007–2018) provides an opportunity to use historical medical data to generate short-term, personalized fracture risk predictions for individual patients. We used the Optum® dataset to develop Crystal Bone, a method that applies machine learning techniques commonly used in natural language processing to the temporal nature of patient histories in order to predict fracture risk over a 1- to 2-year timeframe. Specifically, we repurposed deep-learning models typically applied to language-based prediction tasks in which the goal is to learn the meanings of words and sentences to classify them. Crystal Bone uses context-based embedding techniques to learn an equivalent “semantic” meaning of various medical events. Similar to how language models predict the next word in a given sentence or the topic of an overall document, Crystal Bone can predict that a patient’s future trajectory may contain a fracture or that the “signature” of the patient’s overall journey is similar to that of a typical fracture patient. We applied Crystal Bone to two datasets, one enriched for fracture patients and one representative of a typical hospital system. In both datasets, when predicting likelihood of fracture in the next 1–2 years, Crystal Bone had an area under the receiver operating characteristic (AUROC) score ranging from 72% to 83% on a test (hold-out) dataset. These results suggest performance similar to that of FRAX and Garvan, which have 10-year fracture risk prediction AUROC scores of 64.4% +/- 3.7%.3 Our results suggest that it is possible to use each patient’s unique medical history as it changes over time to predict patients at risk for fracture in 1–2 years. Furthermore, it is theoretically possible to integrate a model like Crystal Bone directly into an EHR system, enabling “hands-off” fracture risk prediction, which could lead to improved identification of patients at very high risk for fracture.

1Kanis JA, Osteoporos Int. 2012;23:2239–56. 2Rubin KH, J Bone Miner Res. 2013;28:1701–17. 3Leslie WD, Osteoporos Int. 2014;25:1–21.

<![CDATA[MON-383 A Study on the Oral Vitamin D Supplementary Treatment of Korean Children and Adolescents]]> Purpose: Between 2017 and 2018, the prevalence rate of vitamin D deficiency (VDD) among children and adolescents in Korea (single institution) was 68.4 percent (59.6 percent for males and 72.5 percent for females). However, effective vitamin D supplements are not consistent in literature. We tried to find out about the dosage and the duration of the administration. Methods: The study was conducted on 2,770 children aged 0-18 who tested serum vitamin D concentrations for outpatients and inpatients at our hospitals from August 2017 to July 2019. One group was treated with maintenance doses and the other group was treated with maintenance doses after oral vitamin D 2000 IU/d for six weeks. The maintenance dose was 400 IU/d before puberty and 1000 IU/d after puberty. Results: There was a significant correlation between serum 25(OH) vitamin D concentration and gender, age, season, weight SDS and BMI SDS (p=0.000, p=0.000, p=0.000, p=0.000, p=0.002, respectively). After 6 months of oral Vitamin D treatment, serum 25 (OH) Vitamin D concentration was increased in both groups (p=0.000, p=0.000, respectively). In a group treated with maintenance doses after oral vitamin D 2000 IU/d for six weeks, it was found a higher rate of change to vitamin D sufficiency (p=0.000). Conclusions: The prevalence rate of VDD increases in female, older age, overweight and winter. The serum 25 (OH) vitamin D concentration increased in both groups after 6 months of treatment. In VDD children, It seemed appropriate to take an oral Vitamin D 2000 IU/day for 6 weeks before maintenance treatment according to the current guideline treatment.

<![CDATA[MON-377 Fracture Site in High-Energy Trauma Is Associated with Osteoporosis Risk]]> Background: In our recent studies, we noted that patients with history of high energy fractures commonly have underlying endocrine abnormalities and low bone mineral density (BMD). In this expanded patient population, we aimed to investigate whether the fracture site can better predict the risk of abnormal BMD.

Methods:We prospectively enrolled adult patients of both genders, with any history of high energy fracture. We measured serum PTH, vitamin-D and calcium and we performed BMD measurements with a DEXA scan. We split our subjects’ BMD, based on the lowest T- or Z-score in “Normal” (≥-0.9), “low bone mass” (LBM) (-1.0 to -2.4) and “Osteoporosis” (OST) (≤-2.5). We classified our patients according to fracture site, in vertebral, humeral, hip, tibial, malleolar-carpal, radial-ulnar and others, including rib fractures. Ratios were compared with χ 2 test, and continuous variables with one-way ANOVA.

Results: We enrolled 444 consecutive subjects with 543 fractures. n=315 (71.0%) subjects had low BMD: OST 25.9% and LBM 45.1%. Among subjects <50 years of age, 43.1% had LBM and 9.2% OST, while in those >50, 46.3% had LBM and 36.6% OST (p<0.0001). The cohort’s mean lowest T/Z score was -1.6±1.2. Subjects with >1 fracture had more frequently low T/Z score (p=0.015). History of vertebral fractures provided the lowest mean T/Z score overall (-2.4±1.1), in females (-2.5±0.9) and subjects >50 (-2.5±1.1). The same holds true for hip fractures in males (-1.9±1.2) and subjects <50 (-2.1±1.4). Subjects with vertebral fractures had the lowest Hip (-1.7±1.2) and Spine (-2.3±1.2) T/Z scores, while those with tibial fractures had the lowest Radius T/Z score (-1.8±1.3). History of vertebral fractures was associated with the highest rate of OST (65.9%) in our overall population, males (50%), females (67.5%), subjects >50 (70.0%), while subjects with history of tibial fractures had the highest rate of normal BMD (46.2%), in males (80%) and females (50.4%), and those <50 (75.0%). Vitamin-D deficiency was present in 81.4% of all subjects. PTH was significantly higher in patients with OST compared to LBM or normal BMD (p=0.0006).

Discussion: Patients with history of high energy fractures need to be screened with DEXA scan early, as they have high likelihood to suffer from osteoporosis.

<![CDATA[MON-LB74 The Problem of Measuring 1,25(OH)2 Vitamin D in Patients With High Levels of 25(OH) Vitamin D]]> Recently, the use of Vitamin D in high doses for treatment of several conditions, mainly autoimmune in nature, has been advocated with dubious results. Hypercalcemia is an important side effect of this intervention. Here we describe our findings in samples that presented 25(OH)D in excess of 150 ng/mL (375 nmol/L) and had 1,25(OH)2D also measured.

Material and Methods: we used serum samples from our diagnostic routine, received for measurement of 25(OH)D and 1,25(OH)2D according to medical requisition. A first group (group A) included 213 samples collected up to November 2018, used Diasorin’s chemiluminescent assays for 25OHD and 1,25(OH)2D, and a second group (group B), comprising 88 samples, used the same 25(OH)D assay and LC-MS/MS method for 1,25(OH)2D.

1,25(OH)2D measurement in the group A used a chemiluminescent competitive assay (Liason XL, Diasorin). The 1,25(OH)2D LC-MS/MS assay includes a previous sample prep, extraction, derivatization and chromatrography. APCI+ is followed by SRM (Selected Reaction Monitoring) and CAD (Collision Activated Dissociation) fragmentation. Precision studies showed, between run CVs of 6.8% to 7.4% and within run of 2.9% to 5.5%.

In vitro investigations testing standards and spiked samples with 25(OH)D3, 25(OH)D2, 3-epimer-25(OH)D3 and 24R,25(OH)2D3 were also used to verify possible analytical interferences in the 1,25(OH)2D LC-MS/MS.

Results: in group A, 25(OH)D median was 371 ng/mL (928 nmol/L), range 154 ng/mL to 856 ng/mL; 1,25(OH)2D median of 350 pg/mL (875 pmol/L), range 41 pg/mL to 1280 pg/mL. Correlation (Spearman) between 25(OH)D and 1,25(OH)2 was r= 0.8649 (P<0.001). In group B, 25(OH)D showed a median of 349 ng/mL (872 nmol/L), range 171 to 756 ng/mL; 1,25(OH)2D median of 54 pg/mL (135 pmol/L), range 24 pg/mL to 108 pg/mL. Correlation between 25(OH)D and 1,25(OH)2 was r= 0.185 (P= 0.08).

In group A 189 samples had calcium measurement (median 9.7 mg/dL, range of 8.7 to 13.6 mg/dL), 182 creatinine (median of 0.8 mg/dL range of 0.3 to 1.8 mg/dL) and 179 PTH (median 19 pg/mL, range 5 to 68 pg/mL). In group B 75 cases had measurements of calcium (median 9.7, range 8.6 to 16.6 mg/dL), 75 of creatinine (median 0.8, range 0.3 to 2.5 mg/dL) and 75 of PTH (median 20, range 9 to 49 pg/mL).

The in vitro tests showed a slight interference from 25(OH)D3, 3-epimer-25(OH)D3 and 24R,25(OH)2D3 molecules in the LC-MS/MS method.

Conclusion: our results confirm data already published showing interference of high levels of 25(OH)D in 1,25(OH)2D measured by immunoassay and, in a milder way, by LC-MS/MS (1). V. Care should be taken in the interpretation of 1,25(OH)2D values in samples with high 25(OH)D values.

1. Hawkes CP, Schnellbacher S, Singh RJ, Levine MA. 25-Hydroxyvitamin D can interfere with a common assay for 1,25-dihydroxyvitamin D in vitamin D intoxication. J Clin Endocrinol Metab. 2015; 100:2883-2889.

<![CDATA[MON-388 Total and Free 1,25dihydroxyvitamin D Levels in Postmenopausal Patients with Primary Hyperparathyroidism]]> Background: Vitamin D3 is metabolized to 25-hydroxyvitamin D [25(OH)D] in liver, and only after it goes to kidney is it converted to its biologically active form, 1,25-dihydroxyvitamin D [1,25(OH)2D]. Also, the majority of both total 25(OH)D and 1,25(OH)2D are tightly bound to vitamin D bind protein (DBP) and only a small portion remains in free form. In certain patient populations, like primary hyperparathyroidism (PHPT), concentrations of free vitamin D metabolites may be affected by altered levels of binding protein.

Objective: To evaluate total and free 1,25(OH)2D levels in PHPT patients and healthy controls.

Methods: Thirty female patients with PHPT and 30 healthy age and body mass index (BMI) matched controls were enrolled (57.1 ± 9.8 years and BMI of 32.2 ± 7.2 kg/m2). Serum levels of calcium, intact parathyroid hormone (iPTH), DBP, total 25(OH)D and 1,25(OH)2D levels were examined. Serum free 25(OH)D and 1,25(OH)2D levels were calculated using equations adapted from Bikle et al.

Results: There were no significant differences in age and BMI between groups. Compared to controls, patients with PHPT had lower total 25(OH)D (25.2 ± 7.5 vs. 19.3 ± 6.4 ng/mL; p <0.001) and DBP levels (40.7± 3.1 vs. 36.5 ± 5.7 mg/dL; p <0.001). There were no significant differences in total 1,25(OH)2D levels or calculated free 25(OH)D levels between PHPT patients and controls; but the calculated free 1,25(OH)2D levels were 27% higher in the PHPT patients compared to controls (p<0.001). The calculated free (but not total) 1,25(OH)2D level was inversely correlated with DBP (r=-0.35, p<0.01) and positively correlated with iPTH levels (r=0.33, p<0.01).

Conclusion: Postmenopausal patients with PHPT had lower serum total 25(OH)D, but similar free 25(OH)D levels. In contrast, total 1,25(OH)2D levels did not differ between patients and controls; however, patients had higher free 1,25(OH)2D. Because total 25(OH)D and 1,25(OH)2D levels do not reflect free levels, standard clinical measures of circulating vitamin D may not be an accurate estimate of true vitamin D status in patients with PHPT.

References: Bikle et al. Serum Protein Binding of 1,25-Dihydroxyvitamin D: A Reevaluation by Direct Measurement of Free Metabolite Levels. JCEM 1985;61:969-75.

<![CDATA[MON-382 Bone Quality and Strength in Obese Men with Type 2 Diabetes Mellitus Are Impaired and Negatively Influenced by Adiposity]]> Background: Obesity and type 2 diabetes mellitus (T2DM) are both associated with normal to above average bone mineral density (BMD) but increased risk of fragility fractures. The impact of T2DM on bone mechanical and microarchitectural features in the obese population is unknown. We hypothesize that obese diabetics have lower bone quality compared to obese nondiabetic individuals. In this study, we investigated the microarchitectural features and mechanical properties of bone of obese men with and without T2DM along with the independent predictors of bone strength. Methods: Ninety-seven obese men (BMI >30) aged 35-65 years-old of which 38 had T2DM were included in the analysis. BMD and body composition were evaluated by DXA and bone microarchitecture of the tibia by high-resolution peripheral quantitative computed tomography. Bone strength was assessed by micro finite element analysis-derived parameters as failure load (f. load) and stiffness. Serum testosterone and estradiol were measured by LC-MS. Serum SHBG, osteocalcin (OCN), C-telopeptide (CTx) and sclerostin (SCL) were measured by ELISA. Results: OCN is lower in obese men with T2DM compared to those without T2DM (4.8 ± 2.8 vs 6.2 ± 2.6 ng/mL p=0.03, respectively), with also a trend for reduced CTx and SCL in the former. BMD at all sites was reduced in obese men with T2DM, but there were no differences in body composition. Obese diabetics also had lower tibial total volumetric BMD (vBMD) (p=0.04) and trabecular vBMD (p=0.01) with greater trabecular spacing (p=0.005). F. load (13.3 ± 2.1 vs 14.5 ± 2.3 kN, p= 0.02) and stiffness (24.7± 4.2 vs 27 ± 4.6 kN/mm, p=0.02) were reduced in men with T2DM relative to men without T2DM, respectively. F. load and stiffness were positively correlated with BMD at all sites, fat free mass (FFM), lean mass, free testosterone, free estradiol and SCL, but negatively correlated with % total body fat and visceral adipose tissue (VAT). FFM, BMD of the total hip, femoral neck and lumbar spine and free testosterone were significant independent predictors of bone strength in the entire group (model: R2: 65.01 p< 0.0001 for f. load and model: R2:63.21 p < 0.0001 for stiffness), whereas age and lumbar spine BMD were found to be independent predictors of bone strength in the non-diabetic group (model R2: 54.6 p< 0.0001 for both f. load and stiffness). Analysis limited to the diabetic subgroup showed that BMD at the femoral neck and total hip, % total body fat, VAT volume, SCL and free estradiol were independent predictors of bone strength (model: R2: 88.4 and p< 0.0001 for f. load and model: R2: 85.3 and p<0.0001 for stiffness). Interleukin-6 was comparable between groups. Conclusions: Obese men with T2DM have lower bone formation and impaired bone quality and strength compared to those without T2DM. In addition to BMD and gonadal hormones, adiposity is an important predictor of bone strength in obese men with T2DM.

<![CDATA[OR13-06 Implementation of a High-Risk Fracture Program in an Integrated Healthcare Delivery System]]> BACKGROUND: Fracture events in older adults are important opportunities for secondary prevention. In response to national (HEDIS) quality metrics in 2008, our medical group implemented a fracture prevention program, identifying women age ≥65y who experienced a fracture and targeting them for osteoporosis screening or treatment within six months. In 2015, we added an outreach program for “high-risk secondary fracture prevention” targeting women age 60-85y and men age 70-85y for osteoporosis therapy within 6 months after a hip, pelvic, humerus, wrist or vertebral fracture. This study examines whether targeting “high-risk fracture” in women and men results in higher treatment rates following a non-vertebral major osteoporotic fracture.

METHODS: This retrospective study was conducted using data from women age 60-85y and men age 70-85y who experienced a fracture of the hip, humerus, and wrist in 2013-2014 (Cohort 1, the era of our HEDIS-only program) or 2015-2016 (Cohort 2, the era of our added “high-risk secondary fracture prevention” program). We excluded patients with primary bone disorders or metastatic cancer and those with osteoporosis treatment in the year prior to fracture. Osteoporosis drug therapy (oral/IV bisphosphonates, denosumab, raloxifene or teriparatide) initiated within six months after the fracture date was assessed. Differences between groups were compared using the chi-squared test, and multivariable logistic regression was used to examine predictors of treatment.

RESULTS: There were 5727 (Cohort 1) and 6469 (Cohort 2) adults identified with hip, humerus, or wrist fracture (high risk fracture). Wrist fracture was the most prevalent fracture in women and hip fracture the most prevalent in men. Osteoporosis treatment initiation within 6 months of the fracture date was achieved for 38% of women and 13% of men in Cohort 1 and 37% of women and 25% of men in Cohort 2. Among women age 60-64, treatment increased from 14% (Cohort 1) to 25% (Cohort 2). Overall, fracture in the later era (2015-2016) was associated with a slightly lower odds of post fracture treatment initiation (adjusted odds ratio OR 0.8, 95% confidence interval (CI) 0.7-0.9) in women 65-85y; however, a much higher odds of treatment was seen (OR 2.3, 95% CI 1.9-2.9) for men 70-85y. Older age, hip fracture, and past osteoporosis therapy were also associated with greater odds of treatment within 6 months.

CONCLUSION: Targeted high-risk fracture intervention resulted in a 2-fold increase in osteoporosis treatment after major non-vertebral osteoporotic fracture in men 70-85y and women 60-64y, the demographic subgroups not previously targeted by HEDIS-based intervention. However, treatment of fractures in women already targeted by HEDIS-based intervention did not increase. Future studies should address potential barriers to treatment and assess the impact of added high-risk fracture outreach on adherence to therapy.

<![CDATA[OR13-05 Romosozumab Treatment Lowers the Incidence of New Vertebral Fractures Across All Fracture Severity Grades Among Postmenopausal Women with Osteoporosis]]> Vertebral fractures (VFx) are the most common type of fracture in postmenopausal osteoporosis (PMO). VFx are generally classified using the Genant grading system as mild (grade 1), moderate (grade 2), or severe (grade 3) according to their degree of compression visualized on spinal x-rays. Regardless of their severity, VFx are associated with significant morbidity and carry the highest subsequent fracture rate of any fragility fracture. We assessed the incidence of new VFx by Genant severity grade in the romosozumab (Romo) vs placebo (Pbo) or alendronate (ALN) arms of the FRAME and ARCH studies, respectively.

In FRAME, 7,180 women with PMO were randomized 1:1 to receive monthly Romo 210 mg or Pbo for 12 months followed by biannual denosumab (DMAb) 60 mg (Romo→DMAb or Pbo→DMAb) for 12 months. In ARCH, 4,093 women with PMO and ≥ 1 fracture were randomized 1:1 to receive monthly Romo 210 mg or weekly oral ALN 70 mg for 12 months followed by ALN 70 mg (Romo→ALN or ALN→ALN) for ≥ 12 months. Throughout both studies, lateral radiographs of the spine were assessed for the presence and severity (mild, moderate, or severe) of VFx using the Genant grading at baseline and after 12 and 24 months of treatment.

The incidence of new VFx was significantly lower among patients who received Romo during the 12-month double-blind treatment phase in both studies. Over 12 months, the incidence of new VFx was 0.5% Romo vs 1.8% Pbo (P<0.001) in FRAME and 3.2% Romo vs 5.0% ALN (P=0.008) in ARCH. Over 24 months, the incidence of new VFx was 0.6% Romo→DMAb vs 2.5% Pbo→DMAb (P<0.001) in FRAME and 4.1% Romo→ALN vs 8.0% ALN→ALN (P<0.001) in ARCH. Fewer new VFx were observed in the Romo arm of both studies across all fracture severity grades. Specifically, in FRAME, the incidence of mild VFx was 0.2% Romo vs 0.4% Pbo over 12 months and 0.2% Romo→DMAb vs 0.6% Pbo→DMAb over 24 months; the incidence of moderate VFx was 0.1% Romo vs 0.9% Pbo over 12 months and 0.2% Romo→DMAb vs 1.4% Pbo→DMAb over 24 months; and the incidence of severe VFx was 0.2% Romo vs 0.5% Pbo over 12 months and 0.2% Romo→DMAb vs 0.6% Pbo→DMAb over 24 months. Similarly, in ARCH, the incidence of mild VFx was 0.5% Romo vs 1.0% ALN over 12 months and 0.4% Romo→ALN vs 1.4% ALN→ALN over 24 months; the incidence of moderate VFx was 1.3% Romo vs 2.1% ALN over 12 months and 1.8% Romo→ALN vs 3.4% ALN→ALN over 24 months; and the incidence of severe VFx was 1.5% Romo vs 1.9% ALN over 12 months and 1.9% Romo→ALN vs 3.3% ALN→ALN over 24 months.

In conclusion, Romo administered over 12 months to women with PMO resulted in reductions in VFx across all fracture severity grades compared with Pbo and standard-of-care ALN. The treatment effect of Romo continued after patients transitioned to an antiresorptive agent. These data will help to foster treatment decisions in postmenopausal women at high risk for VFx.

<![CDATA[MON-394 Vitamin D Levels and Functional Recovery Following Hip Fracture]]> Background: Vitamin D deficiency is common in patients presenting with low energy hip fractures. The relationship between Vitamin D levels at the time of a fracture with long term functional outcomes has not been studied. Identifying a benefit to recovery with adequate vitamin D would support supplementation in elderly patients at risk for hip fracture.

Methods: A retrospective cohort of patients >/= 50 years, who were treated surgically for low energy hip fracture between July 1 2016 and June 30 2018 were identified. The correlation between Vitamin D levels and functional recovery, assessed using the time up and go (TUG) test, survival at 3 months and 1 year, and readmission within 3 months was examined. The Charlson comorbidity index (CCI) at baseline was also assessed.

Results: A total of 216 patients were treated for a hip fracture of which 174 were included with measured baseline Vitamin D levels. A majority were female (112, 64.4%), mean age 79.6 years (+/-11.9), mean Vitamin D level 28.2 ng/ml (+/- 12.4) and mean CCI 5.9 (+/- 2.5). Vitamin D <20 ng/ml was seen in 39 (22.4%) patients and all received appropriate supplementation. 39 (22.4%) individuals died within a year of surgery, among whom 17 (43.6% of 39) passed away within 3 months. 36 (20.7%) were readmitted within 3 months of surgery and 14 (8%) sustained a second fracture within a year. The correlation of Vitamin D levels, taken as a continuous variable, to outcomes, was analyzed using logistic regression. Although not significant, higher Vitamin D was found to be protective against death within 3 months (OR=0.995, p=0.8), but actually increased the odds of death within 1 year (OR=1.008, p=0.62), readmission within 3 months (OR=1.001, p=0.96), second fracture within 1 year (OR=1.017, p=0.33) and failure to recover (OR=1.002, 0.86). After adjusting for age, gender and CCI, Vitamin D levels were non-significantly inversely associated with both TUG 1 and TUG2, with every 1 unit higher Vitamin D associated with a TUG lowered by 0.15 seconds, p=0.42 and 0.44. Vitamin D was poorly correlated to CCI with correlation coefficient of 0.02, p = 0.71.

Conclusions: Our results indicate that Vitamin D levels at the time of a hip fracture do not correlate with patients’ functional outcomes. It is possible that replacing vitamin D eliminated the possible negative impact on functional recovery.

<![CDATA[MON-381 Endocrinological Evaluation of Adult Thalassemia Patients]]> Background: Endocrine disorders are among the most common complications in thalassemia patients. Although cardiac complications are the main cause of mortality, endocrinological disturbances have a significant impact on morbidity and quality of life. Methods: Sixty-eight patients (35 F, 33 M; 60 thalassemia major, 8 thalassemia intermedia) admitted to our outpatient clinic between August 2015 - December 2017 were included in the study. Patients were evaluated for short stature, hypogonadism, glycemic abnormalities, hypoparathyroidism, hypothyroidism and osteoporosis. Results: The average height of thalassemia major patients was 165.67±8.8 cm in men and 155.6±6.6 cm in women. Nine patients had short stature (4 F, 5 E), but 91.5% (54/59) of the whole group had low IGF-1 levels. There were 23 thalassemia major patients (11 F, 12 M) who had a history of hormonal induction therapy for delayed puberty. Overall, 60% (n = 36) of the patients were currently receiving hormone replacement therapy for central hypogonadism (19 F, 17 M). The median age at diagnosis of central hypogonadism was 22.5 years in men (IQR: 16.5-27.5) and 18 years in women (IQR: 16-25). There were five diabetic thalassemia major patients in study group whose median age at diagnosis was 20 (16-36). Of the 47 patients who underwent OGTT, 13 thalassemia major patients had prediabetes (27.7%). None of the thalassemia intermedia patients had glycemic abnormalities. Subclinical hypothyroidism was present in 19.7% (13/66) of the whole group, hypoparathyroidism was found in 8.5% (9/59) of thalassemia major patients, and vitamin D deficiency (25OH D < 20 ng/ml) was found in 70.8% (46/65) of all patients. Of 64 patients who underwent BMD, 25 had osteoporosis (39.1%) while 23 hadosteopenia (35.9%). The incidence of pathological fractures in thalassemia major patients was 20% (11/55). Conclusions: The incidence of endocrine disorders may increase in thalassemia patients due to prolonged duration of lifespan. Regular screening for newly emerging endocrinopathies during adulthood has great value. In our study, the most common endocrine disorders were vitamin D deficiency, hypogonadism, osteoporosis and glycemic abnormalities; respectively. Early diagnosis and treatment would prevent patients from having related morbidities and therefore increase quality of life.

<![CDATA[MON-396 A Critical Review of the Assessment of Vitamin D Status]]> In the United State the evaluation of osteoporosis frequently includes an assessment of vitamin D status. Most often this is done by evaluation of the serum 25 hydroxycalciferol (25 OHD) level. The reasons for this are not entirely clear since D deficiency is characterized by osteomalacia, pathologically very different from osteoporosis. Presumably the reason is to assess the adequacy of calcium absorption across the gastrointestinal mucosa so as to provide sufficient substrate to the osteoid for bone mineralization. If this is the case, the best assessment of D status should be the active metabolite, 1,25 dihydroxycalciferol, (1,25 OH2 D), not an inactive intermediate, such as 25 OHD. The use of an inexact test results in increased cost for less reliable data and supports factitious deficiency with unnecessary and potentially dangerous treatment. The most often quoted reason for not using the 1,25 OH2 D is the short half life. This neglects the fact that half life is not relevant to substances in equilibrium and that the circulating half life does not necessarily reflect the physiologic half life. Equally important, the 25 OHD as a marker of D status is variable due to, among others, drug metabolites affecting hepatic 25 hydroxylases, hepatic function in general, and differences in the activation of of 25 D related to renal function. Additionally, there is virtually no data about the whole body load for any metabolite in the D pathway, so there is no way of actually assessing whether stores are replete or not. While there are several studies suggesting 25 OHD is only a marginal indicator of D status, primarily in the extreme deficiency states which generally rare in the United States. Well controlled studies of the efficacy of 1,25 OH2 D in the assessment of D status are few for many reasons, most prominently cost and lack of sponsor interest. In the absence of such data, one must rely on basic physiologic principals which strongly suggest abandoning the use of the 25 OH D level as an indicator of vitamin D status and, perhaps, using the 1,25 OH2 D to assess D status.

<![CDATA[MON-378 Efficacy and Safety of Romosozumab vs Alendronate Is Similar Across Different Levels of Renal Function Among Postmenopausal Women with Osteoporosis]]> Postmenopausal women with osteoporosis may also have renal insufficiency. We conducted a post hoc analysis of the ARCH study to determine the efficacy and safety of romosozumab (Romo) vs alendronate (ALN) among patients with different levels of baseline renal function.

In ARCH, 4,093 postmenopausal women, 55–90 years old, were randomized 1:1 to receive monthly subcutaneous Romo 210 mg or weekly oral ALN 70 mg for 12 months (double-blind phase [DBP]). Eligible patients had a bone mineral density (BMD) T score of ≤ –2.5 at the total hip (TH) or femoral neck (FN) and either ≥ 1 moderate/severe vertebral fracture (VFx) or ≥ 2 mild VFx; or a T score of ≤ –2.0 at the TH or FN and either ≥ 2 moderate/severe VFx or an Fx of the proximal femur sustained 3–24 months before randomization. Pts were excluded for significantly impaired renal function (eGFR < 35 mL/min/1.73 m2, calculated using the MDRD equation). For the current analysis, patients were categorized by baseline eGFR: normal renal function (eGFR ≥ 90), mild renal insufficiency (eGFR 60–89), or moderate renal insufficiency (eGFR 30–59). The least squares mean (LSM) % change from baseline in BMD at the lumbar spine (LS), TH, and FN; incidence of new VFx; incidence of adverse events (AEs); and changes in renal function were assessed for each eGFR category at month 12 of the DBP.

At baseline, 15% of patients had eGFR ≥ 90, 60% had eGFR 60–89, 24% had eGFR 30–59, and 0.3% had eGFR 15–29. In the overall patient population, LSM % change (95% CI) from baseline in BMD (Romo vs ALN) was 13.7% (13.4–14.0) vs 5.0% (4.7–5.2) for LS, 6.2% (5.9–6.4) vs 2.8% (2.7–3.0) for TH, and 4.9% (4.7–5.2) vs 1.7% (1.5–2.0) for FN (P < 0.001 at each site). Changes in BMD were similar irrespective of baseline eGFR. Among patients with eGFR ≥ 90, eGFR 60–89, and eGFR 30–59, the incidence of new VFx (Romo/ALN) was 3.3%/7.3% (relative risk reduction [RRR] = 57%; 95% CI: 1–81), 3.2%/3.9% (RRR = 19%; 95% CI: -28–49), and 3.4%/6.2% (RRR = 51%; 95% CI: 5–75), respectively. The incidences of AEs, serious AEs, and fatal AEs were similar in both treatment groups within each eGFR category as well as across eGFR categories; there was a higher incidence of positively adjudicated cardiovascular events in the Romo vs ALN group overall and across eGFR categories. One patient in the Romo group with eGFR 60–89 at baseline and 1 in the ALN group with eGFR ≥ 90 at baseline had an AE of mild hypocalcemia. Similar percentages of patients in the Romo and ALN groups had changes in renal function over 12 months of treatment.

In conclusion, the efficacy and safety of Romo vs ALN was similar across different levels of renal function.

<![CDATA[MON-391 Implementation of an Osteoporosis Risk Assessment Instrument (ORAI) to Increase Referral Rates for DEXA Scanning in the Primary Care Setting]]> Abstract

Background/Purpose: Osteoporosis (OP)was first identified and named by healthcare professionals in the 18th century. Today, OP is still the source of fractures which impair mobility, leading to sub-acute stays at rehabilitation centers. A major obstacle is that primary care providers (PCPs) fail to identify warning signs of OP, and inform patients that Dual Energy X-Ray Absorptiometry (DEXA) scans that are one of the best procedures to assess bone health. This project addressed the issue of low rate of referrals for DEXA scans. Theoretical Framework: The Knowledge-to-Action (KTA) model was used to guide this study. Intervention: Implementation of osteoporosis risk assessment instrument. Methods (Design, Sample, Setting, Measures, Analysis): This includes pre-implementation phase, patients’ charts were reviewed; post-implementation phase, the number of people referred to have DEXA scans were analyzed; the evaluation phase, results compared to the previous data. The project focus exclusively on women and men ages 50 to 89 years in two primary care offices in New Jersey. Descriptive analyses concentrated on whether or not ORAI was the tool to increase DEXA scans. Results: The data analysis reflected that the baseline referral rates increased from 1.3 % to 42 % and patients who scored high on the risk assessment instrument have been referred more often than not. Moreover, patients who are at risk and younger than 65 years of age, risk assessment tools led to a positive referral for a DEXA scan. Those who are older than 65 years, risk assessment tools like ORAI should be given with fracture risk assessment tools. This is especially the case when dealing with men, a demographic group often overlooked in the fight against OP. Conclusions Implications: If this project is to be applied at other clinics, more and more patients would be referred, raising awareness of the medical benefits of early detection. Reasonably, covering a broader section of patients, earlier in their lives, will increase clinical income, bringing more patients to primary care offices.

<![CDATA[MON-390 Vitamin D Metabolism in Patients with Acromegaly: A Case-Control Pilot Study]]> Objective: to study the differences in the metabolism of vitamin D and calcium-phosphorus metabolism in patients with an active phase of acromegaly in comparison with healthy individuals. Materials and methods: The study included 8 patients with an active acromegaly, median age 36.5 ± 6.25 years, BMI 27.9 ± 1.95 kg/m2, IGF-1 907.3 ± 239 ng/ml, as well as 8 conditionally healthy individuals selected by age, sex and level of 25(OH)D determined by the immunochemiluminescent method (DEQAS certified). All participants were tested for calcium-phosphorus metabolism, PTH, and vitamin D metabolites by HPLC/MS-MS (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3 and 24,25(OH)2D3) before oral administration of 150 000 IU of an aqueous solution of cholecalciferol and 7 days after administration. Results: In the Acromegaly group, on the 7th day after taking the drug, there was a statistically significant increase in 25(OH)D3 (89.8 ± 10.5 vs. 54.1 ± 14.8 nmol/L), 3-epi-25(OH)D3 (9.0 ± 2.6 vs. 3.3± 1.1 nmol/L) and 24,25(OH)2D3 (8.3 ± 1.9 vs. 6.4 ± 2.1 nmol/L), and a decrease of 25(OH)D2 (0.8 ± 0.2 vs. 1.1 ± 0.3 nmol/L) and a ratio of 24,25(OH)2D3 to 25(OH)D3 (0.1 ± 0.02 vs. 0.13 ± 0.03). A statistically significant increase in albumin-adjusted calcium was also noted (2.39 ± 0.14 vs. 2.31 ± 0.13 mmol/L). The medians of the levels of PTH and phosphorus initially were 27.1 ± 13.5 pg/ml and 1.6 ± 0.3 mmol/l and did not change by day 7 after taking the drug; creatinine and magnesium levels also remained the same. The level of calcium-creatinine ratio in a single portion of urine (CCR) was initially within the reference interval for all patients, its median did not change by day 7, however, in two patients there was a clinically insignificant increase higher than the upper limit of the reference interval; the phosphorus-creatinine ratio in a single portion of urine increased significantly. In the control group, after taking cholecalciferol similar changes in the levels of the studied vitamin D metabolites were observed, the levels of PTH also remained the same, however, there were no changes in the median biochemical parameters of blood and urine by day 7 after drug intake. Among the studied vitamin D metabolites, there were initially no significant differences between the groups; on day 7 a difference was recorded for the level of 3-epi-25(OH)D3 (9.0 ± 2.6 in the Acromegaly group vs. 18.8 ± 8.9 nmol/L in the control group). Among the biochemical parameters in the Acromegaly group higher levels of ionized blood calcium (1.14 ± 0.05 vs 1.1 ± 0.03 mmol/L), blood phosphorus (1.61 ± 0.26 vs 1.15 ± 0.09 mmol/L) and CCR were observed. Conclusion: Loading dose of cholecalciferol in patients with acromegaly is associated with less production of 3-epi-25(OH)D3, and results in lower inactive fraction of vitamin D than in healthy controls. More studies are needed to evaluate the effect of 1.25(OH)2D3 level on calcium-phosphorus metabolism in acromegaly.