Vitamin D and Calcium in Osteoporosis, and the Role of Bone Turnover Markers: A Narrative Review of Recent Data from RCTs
Abstract
:1. Introduction
1.1. Risk Factors of Osteoporosis
1.2. Diagnosis of Osteoporosis
1.3. Biomarkers
1.4. Treatment
2. Methods
3. Results
3.1. Vitamin D Supplementation
3.1.1. Vitamin D and BMD
3.1.2. Vitamin D and Serum 25(OH)D
3.1.3. Vitamin D and PTH
3.1.4. Vitamin D and Falls
3.1.5. Vitamin D and Bone Turnover Markers
Authors | Country | Study Design | n | Sex (W%) | Age (Mean) | Sample (at Baseline) | Groups | Duration of Intervention | Follow-Up | Dose of Vitamin D, Frequency | Effects on BMD | Effects on 25(OH)D and PTH | Effects on Bone Turnover Indices | Effects on Falls | Other Results |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[18] | Brazil | Double-blind, placebo-controlled trial | 160 | 100 | 59.3 | Postmenopausal women | Intervention group (n = 80) and control group (n = 80) | 9 m | 9 m | 1000 IU | ↑ 25(OH)D ↓ PTH | ↓24.2% in s-CTX, 13.4% in P1NP, and 21.3% | - | ||
[32] | USA | Prospective, randomized, double-blind, placebo-controlled trial | 258 | 100 | 68.2 | Healthy African American women with serum 25(OH)D 20–65 nmol/L | VitaminD3 vs. placebo | 3 y | Every 6 months | Adapted dose to achieve a concentration of 30 mg 25(OH)D in the serum >75 nmol/L | ↑BMD of spinal cord ns change in total BMD | ↑25(OH)D | NR | ns changes in risk of falling | - |
[33] | Denmark | Double-blinded placebo-controlled randomized trial | 81 | 100 | 60–79 | Healthy postmenopausal women with 25(OH)D < 50 nmol/L and PTH> 6.9 pmol/L | Intervention group (n = 40) and control group (n = 41) | 3 m | 3 m | 70 µg (2800 IU) Daily | ↑ at the trochanter and femoral neck | ↑25(OH)D ↑1,25(OH)2D ↓PTH | ns changes in BSAP P1NP Osteocalcin CTx | NR | ↓failure load ↑trapezoidal thickness and ↑estimated bone strength at the tibia |
[34] | Brazil | Double-blind, placebo-controlled trial | 160 | 100 | 58.8 | Individuals with BMD> −1.5 SD | Intervention group (n = 80) and control group (n = 81) | 9 m | 9 m | 1000 IU Daily | NR | ↑25(OH)D in intervention group ↓ in the control group ns change in PTH | NR | ↑ rate of falls (OR: 1.95 95% CI, 1.23–3.08) and recurrent falls (OR 2.8, 95% CI, 1.43–5.50) | |
[35] | USA | Prospective, randomized, double-blind, placebo-controlled trial | 260 | 100 | 68.2 | Postmenopausal women | Intervention group (n = 130) and control group (n = 130) | 3 y | Annually | Adapted dose to achieve a concentration of 75–172 nmol/L (doses of 60, 90, and 120 mg) | ↓ Femoral neck BMD in all groups | ↑25(OH)D | NR | - | |
[36] | USA | Double-blind, placebo-controlled randomized clinical trial | 218 | 100 | 59.6 | Postmenopausal women | Intervention group (n = 109) and control group (n = 109) | 12 m | 12 m | 2000 IU Daily (+ weight loss diet) | ns changes in spine and femoral neck BMD | ↑25(OH)D | ns change in upper body muscle strength ↓leg strength in the vitamin group D compared to placebo | ||
[37] | Finland | Double-blind, placebo-controlled trial | 350 | 100 | 74 | Elderly women | Group a (intervention): n = 102; Group b intervention): n = 103 Group c (intervention):n = 102, and Group d (control): n = 102 | 1 y | 1y, 2 y assessment | 20 μg (800 IU) +/- exercise Daily | ↓ Femoral neck BMD in all groups | ↑25(OH)D | ns change in falls | ||
[38] | Austria | Single-center, double-blind, randomized placebo-controlled trial | 192 | 0 | 43 | Healthy men | Intervention group (n = 100) and control group (n = 100) | 3 m | 3 m | 20,000 IU Weekly | ↓ femoral neck BMD in men with baseline 25(OH)D levels ≥ 50 nmol/L (n = 115) ns changes in total body BMD, lumbar spine BMD, hip BMD | ↑25(OH)D and ns changes in PTH in subjects with 25(OH)D levels < 40 nmol/L ↑25(OH)D and ↓PTH in subjects with 25(OH)D levels > 40 nmol/L | ns changes in CTX, OC | ns changes in BTM, TBS | |
[40] | Great Britain | Single-center, parallel-group, participant-randomized, double-blind interventional trial | 379 | 48 | 75 | Patients in lack of treatment for osteoporosis, hyperparathyroidism, history of fractures, hypercalcemia, hypocalcemia | 3 intervention groups (~110 per group) | 1 y | 1 y | 300 μg 600 μg 1200 μg (12.000, 24.000 and 48.000 IU) Monthly | ns change in bone density | ↑25(OH)D | NR | ns changes in falls | - |
[41] | Canada | Double-blind, randomized clinical trial | 311 | 47 | 62.2 | lumbar spine and total ischial BMD T score >−2.5 SD, serum 25(OH)D: 30–125 nmol/L and normal serum Ca 2.10–2.55 mmol/L | 3 parallel groups and control group (n~100 per group, total n = 400) | 3 y | DXA: 12, 24 and 36 months (HR-pQCT: 6, 12, 24 and 36 months | 400 IU 4000 IU 10,000 IU Daily | ↓ radial BMD at 4000 IU/day or 10,000 IU/day ↓tibial BMD at 10,000 IU per day | ↑25(OH)D ↓PTH | ↑CTx | ns change in falls | ns changes in failure load ns differences in bone strength in either the stapes or the tibia |
[42] | Canada | Randomized clinical trial | 311 | 47 | 62.2 | total hip BMD total hip T score >−2.5 SD, serum 25(OH)D between 30 and 125 nmol/L and serum Ca 2.10–2.55 mmol/L | 3 parallel groups (n~100 per group) | 3 y | DXA: 12, 24, and 36 months (HR-pQCT: 6, 12, 24, and 36 months | 400 IU 4000 IU 10,000 IU Daily | ↓ BMD in women but not men ↓1.8% (400 IU), 3.8% (4000 IU) and 5.5% (10,000 IU) at the radius. Men ↓ 0.9% (400 IU), 1.3% (4000 IU), and 1.9% (10,000 IU) at the radius. In the tibia, losses in tBMD were smaller but followed a similar trend | ↑25(OH)D ns PTH | ns CTx | NR | ns bone strength changes |
[43] | Iran | Single blind Clinical trial | 400 | 48.5 | 20–60 | Healthy adults | Vitamin D (n = 76) | 8 w | 8 w | 50,000 Weekly | ↓ osteoporosis in the intervention group | - | |||
[44] | Shanghai | Randomized, double-blind, Placebo-controlled trial | 448 | 69 | 31.9 | Vitamin D-deficient adults’ serum 25(OH)D: 12.5–50 nmol/L | Placebo (n = 222) Intervention group (n = 226) | 20 w | 20 w | 2000 IU Daily | ↑25(OH)D | ↑bALP ns change in serum PINP, β-CTX, or TRAP5b In intervention group, subjects with 25(OH)D ≥75 nmol/L ↑β-CTX and TRAP5b, but smaller ↓ in Ca and Ca product phosphorus | |||
[46] | Austria | Randomized, double-blind, placebo-controlled trial | 289 | 37.5% control g and 35.3 vitamin D | 62.2 control and 60.3 vitamin D | Patients in ICU | Placebo (n =136) Vitamin D (n = 153) | 6 m | 6 m | Initial: 540,000 IU 90,000 IU Monthly | ns change in BMD at the lumbar spine and femoral neck | ↑25(OH)D ↓ PTH | ns changes in CTX and OC | ns changes in falls | - |
[47] | New Zealand | Randomized, double-blind, placebo-controlled trial | 452 | 35% control and 38% vitamin d | 69 | Adults living in the community | Placebo (n = 224) Vitamin D (n = 228) | 2y | 2y | 100,000 IU (2.5 mg) Monthly First dose was double | ns change in lumbar spine BMD ↓ proximal femur and total body BMD in all groups | ↑25(OH)D | |||
[48] | India | Controlled trial | 16 | 0 | 18–35 | Men with vitamin D deficiency | Intervention group (n = 8 and a control group (n = 4) | 3 y | 3 y | 60,000 IU Weekly | ↑25(OH)D | ↑ Bone mineral balance | |||
[49] | Austria | Single-center, double-blind, placebo-controlled, parallel-group study | 197 | 47 | 62.4 | People with arterial hypertension and serum 25(OH)D concentration <75 nmol/L | Vitamin D (n = 98) Placebo (n = 99) | 8 w | 8 y | 2800 IU | ns changes in bALP, CTX, OC and P1NP values ↑ OC in men. | - |
3.2. Combined Vitamin D and Ca Supplementation
3.2.1. Combined Vitamin D, Ca Supplementation, and BMD
Authors | Country | Study Design | n | Sex (WM %) | Age (Mean) | Sample (at Baseline) | Groups | Duration of Intervention | Follow-Up | Dose of Vitamin D, Frequency | Effects on BMD | Effects on 25(OH)D and PTH | Effects on Bone Turnover Indices | Effects on Falls | Secondary Results |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[21] | Australia | Randomized placebo-controlled doubled-blind RCT | 54 | n/a | 32 | Overweight or obese vitamin D-deficient (25OHD < 50 nmol/L) adults | Vitamin D n = 28 placebo group n = 26 | 16 weeks | 16 weeks | Loading dose of 100.000 IU cholecalciferol, followed by 4000 IU cholecalciferol/d or a matching placebo | ns changes in BMD | ↑25(OH)D ↓ PTH | ns changes in FGF-23 | ns change in OF | |
[24] | China | randomized controlled trial | 420 | 81.4 | >60 | bone mineral density (BMD) at lumbar vertebra or hip ≤ −2.5 | Inactive vitamin group (n = 98) Inactive vitamin with exercise group (n = 97) Active vitamin group (n = 99) Active vitamin and exercise group (n = 98) | 12 m | 3,6,12 m 12 m BMD | Inactive VitD group: 800 mg Ca and 800 IU inactive VitD/day. Inactive VitD + exercise group: 800 mg Ca and 800 IU VitD/day + instructions to improve muscle strength and balance Active VitD group: 800 mg Ca and 0.5 µg active VitD/day Active VitD + exercise group: 800 mg Ca and 0.5 µg of active VitD/day + instructions for improving muscle strength and balance | ↑Lumbar BMD of the A VitD group and the P-A VitD group Ns change in hip, femur neck BMD | ↑25(OH)D | ns change in OF ns change in falls | - | |
[25] | Turkey | Prospective, open-label, controlled clinical trial. | 120 | 100 | 50 | Pre- and postmenopausal women diagnosed with vitamin D deficiency | Group A (cholecalciferol + Ca) n = 43 Group B (calcitriol + cholecalciferol + Ca) n = 77 | 6 m | 6 m |
Group A (1000 IU of Vitamin D3 and 1 g of Ca/D) Group B (0.5 μg calcitriol in addition to 400 IU of cholecalciferol and 1 g of Ca/D) | Ns in total BMD ↑ Lumbar spine BMD in group B | ↑25(OH)D ↓PTH |
↓
ALP (Group B) ↑ CTx, NTx, deoxypyridinoline, OC (Group A and Group B, no difference between groups) | ns change in OF | - |
[26] | USA | Randomized double-blind, controlled trial | 222 | 99 | 71 | Elderly (>65 years), overweight with a serum 25(OH)D between 10–30 ng/m | High dose group (n = 110) Low dose group (n = 112) | 6, 12 m | 6,12 m | Supplementation with 1000 mg of elemental Ca citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 | ↑BMD at the total hip and lumbar spine, but not the femoral neck, in both study arms. ↑ subtotal body BMD in the high-dose group at 1 year. Subjects with 25OHD < 20 ng/mL and PTH level > 76 pg/mL ↑ hip BMD | ↑25(OH)D ↑ calcitriol in the high dose group ↓ PTH but ns change between groups | ↓OC, CTX ns difference between groups | ↑ in OF | |
[27] | India | Randomized, open-labeled, comparative, controlled clinical study | 65 | 66 | 40 | Osteopenic adults | Treatment group: 32 Control group: 33 | 0, 6, 12m | 6, 12 m | Treatment group received two tablespoons of PG (10mL in lukewarm milk), along with Ca and vitamin D3 supplements (containing elemental Ca 1200 mg and vitamin D3 [cholecalciferol] 800 IU/day) twice a day, whereas control group received only Ca and vitamin D3 supplements twice a day | ↑BMD scores at 6 months, which was sustained at 12 months in both the study groups. Maximal improvement was observed in the lumbar spine and left forearm regions. | ↑vitamin D3 in the PG group than in the SOC group at 6 and 12 months, which was statistically significant at 12 months (30.3 ng/mL vs. 22.3 ng/mL) | Improvement in OC, TRAP-5b in the PG-treated group | ns change in OF | |
[28] | USA | Randomized, double-blind controlled study | 58 | 100 | 58 | overweight/obese healthy, postmenopausal women (age 50–70 years old; BMI 25–40 kg/m2) |
A: 600 IU/day (n = 19), B: 2000 IU/day (n = 20), C:4000 IU/day (n = 19) | 12 m | 12 m | Vitamin D 600, 2000, 4000 IU Ca 1.2 g/day during weight control | ↓ cortical thickness in the 600-IU group but not in the higher vitamin D groups | ↑25(OH)D ↓ PTH | ↑ CTX, P1NP ns difference between groups | ns change in OF | 3 % weight reduction |
[29] | USA | Randomized trial | 135 | 100 | 55.8 | Overweight/obese Caucasian, early–postmenopausal women | Placebo n = 62 Dairy n = 64 Supplement (Ca + vitamin D) n = 62 | 6 m | 6 m | Moderate energy restriction (~85% of energy needs) for all participants. All subjects complemented with low-fat dairy foods (4–5 servings/day), or Ca + vitamin D supplements a total of ~1500 mg/day and 600 IU/day of Ca and vitamin D, respectively, or placebo pills | Supplement group: lower decrease or slight increase in BMD in measured skeletal sites. | ↑25(OH)D ↓ PTH | ns change in OF | ns change in OC, NTx ↓ Urinary CTx in the supplement group and ↑ in the control group | dairy group: better body composition outcomes, higher decrease in fat and lower decrease in lean mass. |
[30] | USA | Randomized placebo controlled trial | 273 (Caucasian n = 163 African American n = 110) | 100 | Caucasian 67 African American 65 | Elderly women with vitamin D insufficiency, (serum 25(OH)D levels ≤50 nmol/ L) | 8 intervention groups D3 doses of: 400 IU/d, n = 20 800 IU/d, n = 22 1600 IU/d, n = 23 2400 IU/d, n = 24 3200 IU/d, n = 21 4000 IU/d, n = 20 4800 IU/d, n = 21 Placebo group n = 22 | 12 m | 12 m | Vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU daily Ca 200 mg as to maintain a total Ca intake of ~1200 mg | ns change in total BMD and hip, lumbar spine BMD No association between change in BMD and the 12-month values for serum total 25(OH)D, serum free 25(OH)D or serum 1,25(OH)2D | ↑25(OH)D ↓PTH | ns change in OF | Results for Caucasian and African American women were similar. ↑ in total body Ca in the treated women with higher baseline serum PTH. | |
[51] | USA and Lebanon | Double-blind, randomized controlled trial | 221 | 55.2 | >65 71.1 | Overweight, with a baseline serum 25(OH)D of between 10 and 30 ng/mL | High-dose group: 1000 mg elemental Ca and 3750 IU/day vitamin D. Low-dose group: 1000 mg elemental Ca and 600 IU/day vitamin D | 6, 12 m | 6, 12 m | All subjects received 1000 mg elemental Ca and oral vitamin D3 (600 IU/ day or 3750 IU/day) supplementation | ns change in spine and hip BMD at 12 months ↑ subtotal body BMD with the high dose. | No increase in total, bioavailable, and free 25(OH)D levels was found at 12 months (p < 0.001) for low dose and high-dose supplementation. Vitamin D supplementation at a dose of 3750 IU/day resulted in serum levels of total, bioavailable, and free 25(OH)D, that were 1.28–1.38 higher than levels reached with 600 IU/day dose. | Weak but significant relationship between 25(OH)D and % BMD change at femoral neck only (p = 0.033), and only mild significant correlation between the free and bioavailable 25(OH)D, and the total body BMD at 12 months. |
3.2.2. Combined Vitamin D and Ca Supplementation, and Circulating 25(OH)D
3.2.3. Combined Vitamin D and Ca Supplementation, and Circulating Calcium
3.2.4. Combined Vitamin D, Ca Supplementation, and PTH
3.2.5. Combined Vitamin D and Ca Supplementation, and Falls/Fractures
3.2.6. Combined Vitamin D and Ca Supplementation, and Bone Turnover Biomarkers
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
- Rossini, M.; Adami, S.; Bertoldo, F.; Diacinti, D.; Gatti, D.; Giannini, S.; Giusti, A.; Malavolta, N.; Minisola, S.; Osella, G.; et al. Guidelines for the diagnosis, prevention and management of osteoporosis. Reumatismo 2016, 68, 1–39. [Google Scholar] [CrossRef] [PubMed]
- Fitzpatrick, L.A. Secondary Causes of Osteoporosis. Mayo Clin. Proc. 2002, 77, 453–468. [Google Scholar] [CrossRef] [PubMed]
- Ribagin, S.; Roeva, O.; Pencheva, T. Generalized Net model of asymptomatic osteoporosis diagnosing. In Proceedings of the 2016 IEEE 8th International Conference on Intelligent Systems (IS), Sofia, Bulgaria, 4–6 September 2016; pp. 604–608. [Google Scholar]
- Kanis, J.A.; Norton, N.; Harvey, N.C.; Jacobson, T.; Johansson, H.; Lorentzon, M.; McCloskey, E.V.; Willers, C.; Borgström, F. SCOPE 2021: A new scorecard for osteoporosis in Europe. Arch Osteoporos 2021, 16, 82. [Google Scholar] [CrossRef] [PubMed]
- Salari, N.; Ghasemi, H.; Mohammadi, L.; Behzadi, M.H.; Rabieenia, E.; Shohaimi, S.; Mohammadi, M. The global prevalence of osteoporosis in the world: A comprehensive systematic review and meta-analysis. J. Orthop. Surg. Res. 2021, 16, 609. [Google Scholar] [CrossRef]
- Lane, N.E. Epidemiology, etiology, and diagnosis of osteoporosis. Am. J. Obstet. Gynecol. 2006, 194, S3–S11. [Google Scholar] [CrossRef]
- Fischer, V.; Haffner-Luntzer, M.; Amling, M.; Ignatius, A. Calcium and vitamin D in bone fracture healing and post-traumatic bone turnover. Eur. Cell Mater. 2018, 35, 365–385. [Google Scholar] [CrossRef]
- Mithal, A.; Bansal, B.; Kyer, C.S.; Ebeling, P. The Asia-Pacific Regional Audit-Epidemiology, Costs, and Burden of Osteoporosis in India 2013: A report of International Osteoporosis Foundation. Indian J. Endocrinol. Metab. 2014, 18, 449–454. [Google Scholar] [CrossRef]
- Wyskida, M.; Wieczorowska-Tobis, K.; Chudek, J. Prevalence and factors promoting the occurrence of vitamin D deficiency in the elderly. Postep. Hig. Med. Dosw. (Online) 2017, 71, 198–204. [Google Scholar] [CrossRef]
- Holick, M.F.; Binkley, N.C.; Bischoff-Ferrari, H.A.; Gordon, C.M.; Hanley, D.A.; Heaney, R.P.; Murad, M.H.; Weaver, C.M. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2011, 96, 1911–1930. [Google Scholar] [CrossRef]
- Makris, K.; Sempos, C.; Cavalier, E. The measurement of vitamin D metabolites: Part I—Metabolism of vitamin D and the measurement of 25-hydroxyvitamin D. Hormones 2020, 19, 81–96. [Google Scholar] [CrossRef]
- Liu, C.; Kuang, X.; Li, K.; Guo, X.; Deng, Q.; Li, D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Food Funct. 2020, 11, 10817–10827. [Google Scholar] [CrossRef]
- Reid, I.R. Osteoporosis: Evidence for vitamin D and calcium in older people. Drug Ther. Bull. 2020, 58, 122–125. [Google Scholar] [CrossRef]
- Kanis, J.A.; Cooper, C.; Rizzoli, R.; Reginster, J.-Y.; on behalf of the Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos. Int. 2019, 30, 3–44. [Google Scholar] [CrossRef]
- Kanis, J. Assessment of Osteoporosis at the Primary Health-Care Level; World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield: Sheffield, UK, 2007. [Google Scholar]
- Weaver, C.M.; Gordon, C.M.; Janz, K.F.; Kalkwarf, H.J.; Lappe, J.M.; Lewis, R.; O’Karma, M.; Wallace, T.C.; Zemel, B.S. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: A systematic review and implementation recommendations. Osteoporos. Int. 2016, 27, 1281–1386. [Google Scholar] [CrossRef]
- Bieglmayer, C.; Kudlacek, S. The bone marker plot: An innovative method to assess bone turnover in women. Eur. J. Clin. Investig. 2009, 39, 230–238. [Google Scholar] [CrossRef]
- Nahas-Neto, J.; Cangussu, L.M.; Orsatti, C.L.; Bueloni-Dias, F.N.; Poloni, P.F.; Schmitt, E.B.; Nahas, E.A.P. Effect of isolated vitamin D supplementation on bone turnover markers in younger postmenopausal women: A randomized, double-blind, placebo-controlled trial. Osteoporos. Int. 2018, 29, 1125–1133. [Google Scholar] [CrossRef]
- Chavassieux, P.; Portero-Muzy, N.; Roux, J.-P.; Garnero, P.; Chapurlat, R. Are Biochemical Markers of Bone Turnover Representative of Bone Histomorphometry in 370 Postmenopausal Women? J. Clin. Endocrinol. Metab. 2015, 100, 4662–4668. [Google Scholar] [CrossRef]
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Dietary reference values for vitamin D. EFSA J. 2016, 14, e04547. [Google Scholar] [CrossRef]
- Mesinovic, J.; Mousa, A.; Wilson, K.; Scragg, R.; Plebanski, M.; de Courten, M.; Scott, D.; Naderpoor, N.; de Courten, B. Effect of 16-weeks vitamin D replacement on calcium-phosphate homeostasis in overweight and obese adults. J. Steroid. Biochem. Mol. Biol. 2019, 186, 169–175. [Google Scholar] [CrossRef]
- Christakos, S.; Lieben, L.; Masuyama, R.; Carmeliet, G. Vitamin D endocrine system and the intestine. BoneKEy Rep. 2014, 3, 496. [Google Scholar] [CrossRef] [Green Version]
- Cianferotti, L.; Bertoldo, F.; Bischoff-Ferrari, H.A.; Bruyere, O.; Cooper, C.; Cutolo, M.; Kanis, J.A.; Kaufman, J.-M.; Reginster, J.-Y.; Rizzoli, R.; et al. Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: Research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO). Endocrine 2017, 56, 245–261. [Google Scholar] [CrossRef] [PubMed]
- Feng, F.; Shi, G.; Chen, H.; Jia, P.; Bao, L.; Xu, F.; Sun, Q.-C.; Tang, H. Comprehensive Interventions Including Vitamin D Effectively Reduce the Risk of Falls in Elderly Osteoporotic Patients. Orthop. Surg. 2021, 13, 1262–1268. [Google Scholar] [CrossRef] [PubMed]
- Tanakol, R.; Gül, N.; Üzüm, A.K.; Aral, F. Calcitriol treatment in patients with low vitamin D levels. Arch. Osteoporos. 2018, 13, 114. [Google Scholar] [CrossRef] [PubMed]
- Rahme, M.; Sharara, S.L.; Baddoura, R.; Habib, R.H.; Halaby, G.; Arabi, A.; Singh, R.J.; Kassem, M.; Mahfoud, Z.; Hoteit, M.; et al. Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial. J. Bone Min. Res. 2017, 32, 1486–1495. [Google Scholar] [CrossRef]
- Munshi, R.P.; Kumbhar, D.A.; Panchal, F.H.; Varthakavi, P. Assessing the Effectiveness of Panchatikta Ghrita, a Classical Ayurvedic Formulation as Add-on Therapy to Vitamin D3 and Calcium Supplements in Patients with Osteopenia: A Randomized, Open-Labeled, Comparative, Controlled Clinical Study. J. Altern. Complement. Med. 2019, 25, 1044–1053. [Google Scholar] [CrossRef]
- Pop, L.C.; Sukumar, D.; Schneider, S.H.; Schlussel, Y.; Stahl, T.; Gordon, C.; Wang, X.; Papathomas, T.V.; Shapses, S.A. Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial. Osteoporos. Int. 2017, 28, 377–388. [Google Scholar] [CrossRef]
- Ilich, J.Z.; Kelly, O.J.; Liu, P.-Y.; Shin, H.; Kim, Y.; Chi, Y.; Wickrama, K.K.A.S.; Colic-Baric, I. Role of Calcium and Low-Fat Dairy Foods in Weight-Loss Outcomes Revisited: Results from the Randomized Trial of Effects on Bone and Body Composition in Overweight/Obese Postmenopausal Women. Nutrients 2019, 11, 1157. [Google Scholar] [CrossRef]
- Smith, L.M.; Gallagher, J.C.; Kaufmann, M.; Jones, G. Effect of increasing doses of vitamin D on bone mineral density and serum N-terminal telopeptide in elderly women: A randomized controlled trial. J. Intern. Med. 2018, 284, 685–693. [Google Scholar] [CrossRef]
- Weaver, C.M.; Alexander, D.D.; Boushey, C.J.; Dawson-Hughes, B.; Lappe, J.M.; LeBoff, M.S.; Liu, S.; Looker, A.C.; Wallace, T.C.; Wang, D.D. Calcium plus vitamin D supplementation and risk of fractures: An updated meta-analysis from the National Osteoporosis Foundation. Osteoporos. Int. 2016, 27, 367–376. [Google Scholar] [CrossRef]
- Aloia, J.F.; Katumuluwa, S.; Stolberg, A.; Usera, G.; Mikhail, M.; Hoofnagle, A.N.; Islam, S. Safety of calcium and vitamin D supplements, a randomized controlled trial. Clin. Endocrinol. 2018, 89, 742–749. [Google Scholar] [CrossRef]
- Bislev, L.S.; Langagergaard Rødbro, L.; Rolighed, L.; Sikjaer, T.; Rejnmark, L. Bone Microstructure in Response to Vitamin D3 Supplementation: A Randomized Placebo-Controlled Trial. Calcif. Tissue Int. 2019, 104, 160–170. [Google Scholar] [CrossRef] [PubMed]
- Cangussu, L.M.; Nahas-Neto, J.; Orsatti, C.L.; Poloni, P.F.; Schmitt, E.B.; Almeida-Filho, B.; Nahas, E.A.P. Effect of isolated vitamin D supplementation on the rate of falls and postural balance in postmenopausal women fallers: A randomized, double-blind, placebo-controlled trial. Menopause 2016, 23, 267–274. [Google Scholar] [CrossRef] [PubMed]
- Dhaliwal, R.; Islam, S.; Mikhail, M.; Ragolia, L.; Aloia, J.F. Effect of vitamin D on bone strength in older African Americans: A randomized controlled trial. Osteoporos. Int. 2020, 31, 1105–1114. [Google Scholar] [CrossRef] [PubMed]
- Mason, C.; Tapsoba, J.D.; Duggan, C.; Imayama, I.; Wang, C.-Y.; Korde, L.; McTiernan, A. Effects of Vitamin D3 Supplementation on Lean Mass, Muscle Strength, and Bone Mineral Density During Weight Loss: A Double-Blind Randomized Controlled Trial. J. Am. Geriatr. Soc. 2016, 64, 769–778. [Google Scholar] [CrossRef] [PubMed]
- Uusi-Rasi, K.; Patil, R.; Karinkanta, S.; Kannus, P.; Tokola, K.; Lamberg-Allardt, C.; Sievänen, H. A 2-Year Follow-Up After a 2-Year RCT with Vitamin D and Exercise: Effects on Falls, Injurious Falls and Physical Functioning Among Older Women. J. Gerontol. A Biol. Sci. Med. Sci. 2017, 72, 1239–1245. [Google Scholar] [CrossRef]
- Lerchbaum, E.; Trummer, C.; Theiler-Schwetz, V.; Kollmann, M.; Wölfler, M.; Pilz, S.; Obermayer-Pietsch, B. Effects of Vitamin D Supplementation on Bone Turnover and Bone Mineral Density in Healthy Men: A Post-Hoc Analysis of a Randomized Controlled Trial. Nutrients 2019, 11, 731. [Google Scholar] [CrossRef]
- Rangarajan, R.; Mondal, S.; Thankachan, P.; Chakrabarti, R.; Kurpad, A.V. Assessing bone mineral changes in response to vitamin D supplementation using natural variability in stable isotopes of Calcium in Urine. Sci. Rep. 2018, 8, 16751. [Google Scholar] [CrossRef]
- Aspray, T.J.; Chadwick, T.; Francis, R.M.; McColl, E.; Stamp, E.; Prentice, A.; von Wilamowitz-Moellendorff, A.; Schoenmakers, I. Randomized controlled trial of vitamin D supplementation in older people to optimize bone health. Am. J. Clin. Nutr. 2019, 109, 207–217. [Google Scholar] [CrossRef]
- Burt, L.A.; Billington, E.O.; Rose, M.S.; Raymond, D.A.; Hanley, D.A.; Boyd, S.K. Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA 2019, 322, 736. [Google Scholar] [CrossRef]
- Burt, L.A.; Billington, E.O.; Rose, M.S.; Kremer, R.; Hanley, D.A.; Boyd, S.K. Adverse Effects of High-Dose Vitamin D Supplementation on Volumetric Bone Density Are Greater in Females than Males. J. Bone Min. Res. 2020, 35, 2404–2414. [Google Scholar] [CrossRef]
- Shahnazari, B.; Moghimi, J.; Foroutan, M.; Mirmohammadkhani, M.; Ghorbani, A. Comparison of the effect of vitamin D on osteoporosis and osteoporotic patients with healthy individuals referred to the Bone Density Measurement Center. Biomol. Concepts 2019, 10, 44–50. [Google Scholar] [CrossRef] [PubMed]
- Yao, P.; Sun, L.; Xiong, Q.; Xu, X.; Li, H.; Lin, X. Cholecalciferol Supplementation Promotes Bone Turnover in Chinese Adults with Vitamin D Deficiency. J. Nutr. 2018, 148, 746–751. [Google Scholar] [CrossRef] [PubMed]
- Reid, I.R.; Bolland, M.J.; Grey, A. Effects of Vitamin D Supplements on Bone Mineral Density: A Systematic Review and Meta-Analysis. Lancet. 2014, 383, 146–155. [Google Scholar] [CrossRef] [PubMed]
- Schwetz, V.; Schnedl, C.; Urbanic-Purkart, T.; Trummer, C.; Dimai, H.P.; Fahrleitner-Pammer, A.; Putz-Bankuti, C.; Christopher, K.B.; Obermayer-Pietsch, B.; Pieber, T.R.; et al. Effect of vitamin D3 on bone turnover markers in critical illness: Post hoc analysis from the VITdAL-ICU study. Osteoporos. Int. 2017, 28, 3347–3354. [Google Scholar] [CrossRef]
- Reid, I.R.; Horne, A.M.; Mihov, B.; Gamble, G.D.; Al-Abuwsi, F.; Singh, M.; Taylor, L.; Fenwick, S.; Camargo, C.A.; Stewart, A.W.; et al. Effect of Monthly High-Dose Vitamin D on Bone Density in Community-Dwelling Older Adults Substudy of a Randomized Controlled Trial. J. Intern. Med. 2017, 282, 452–460. [Google Scholar] [CrossRef]
- Aloia, J.F.; Rubinova, R.; Fazzari, M.; Islam, S.; Mikhail, M.; Ragolia, L. Vitamin D and Falls in Older African American Women: The PODA Randomized Clinical Trial. J. Am. Geriatr. Soc. 2019, 67, 1043–1049. [Google Scholar] [CrossRef]
- Schwetz, V.; Trummer, C.; Pandis, M.; Grübler, M.R.; Verheyen, N.; Gaksch, M.; Zittermann, A.; März, W.; Aberer, F.; Lang, A.; et al. Effects of Vitamin D Supplementation on Bone Turnover Markers: A Randomized Controlled Trial. Nutrients 2017, 9, 432. [Google Scholar] [CrossRef]
- Elder, C.J.; Bishop, N.J. Rickets. Lancet 2014, 383, 1665–1676. [Google Scholar] [CrossRef]
- Bingham, C.T.; Fitzpatrick, L.A. Noninvasive testing in the diagnosis of osteomalacia. Am. J. Med. 1993, 95, 519–523. [Google Scholar] [CrossRef]
- El Sabeh, M.; Ghanem, P.; Al-Shaar, L.; Rahme, M.; Baddoura, R.; Halaby, G.; Singh, R.J.; Vanderschueren, D.; Bouillon, R.; El-Hajj Fuleihan, G. Total, Bioavailable, and Free 25(OH)D Relationship with Indices of Bone Health in Elderly: A Randomized Controlled Trial. J. Clin. Endocrinol. Metab. 2021, 106, e990–e1001. [Google Scholar] [CrossRef]
- Dominguez, L.J.; Farruggia, M.; Veronese, N.; Barbagallo, M. Vitamin D Sources, Metabolism, and Deficiency: Available Compounds and Guidelines for Its Treatment. Metabolites 2021, 11, 255. [Google Scholar] [CrossRef]
- Goltzman, D. Functions of vitamin D in bone. Histochem. Cell Biol. 2018, 149, 305–312. [Google Scholar] [CrossRef]
- Bolland, M.J.; Grey, A.; Avenell, A. Effects of vitamin D supplementation on musculoskeletal health: A systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol. 2018, 6, 847–858. [Google Scholar] [CrossRef]
- Collins, D.; Jasani, C.; Fogelman, I.; Swaminathan, R. Vitamin D and bone mineral density. Osteoporos. Int. 1998, 8, 110–114. [Google Scholar] [CrossRef]
- Zittermann, A.; Ernst, J.B.; Birschmann, I.; Dittrich, M. Effect of Vitamin D or Activated Vitamin D on Circulating 1,25-Dihydroxyvitamin D Concentrations: A Systematic Review and Metaanalysis of Randomized Controlled Trials. Clin. Chem. 2015, 61, 1484–1494. [Google Scholar] [CrossRef]
- Lotito, A.; Teramoto, M.; Cheung, M.; Becker, K.; Sukumar, D. Serum Parathyroid Hormone Responses to Vitamin D Supplementation in Overweight/Obese Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Nutrients 2017, 9, 241. [Google Scholar] [CrossRef]
- Carter, G.D.; Carter, R.; Jones, J.; Berry, J. How accurate are assays for 25-hydroxyvitamin D? Data from the international vitamin D external quality assessment scheme. Clin. Chem. 2004, 50, 2195–2197. [Google Scholar] [CrossRef]
- Gallagher, J.C.; Sai, A.; Templin, T.; Smith, L. Dose response to vitamin D supplementation in postmenopausal women: A randomized trial. Ann. Intern. Med. 2012, 156, 425–437. [Google Scholar] [CrossRef]
- Ebeling, P.R. Vitamin D and bone health: Epidemiologic studies. BoneKEy Rep. 2014, 3, 511. [Google Scholar] [CrossRef]
- Seamans, K.M.; Cashman, K.D. Existing and potentially novel functional markers of vitamin D status: A systematic review. Am. J. Clin. Nutr. 2009, 89, 1997S–2008S. [Google Scholar] [CrossRef] [Green Version]
- Di Filippo, L.; De Lorenzo, R.; Giustina, A.; Rovere-Querini, P.; Conte, C. Vitamin D in Osteosarcopenic Obesity. Nutrients 2022, 14, 1816. [Google Scholar] [CrossRef] [PubMed]
- Chiodini, I.; Bolland, M.J. Calcium supplementation in osteoporosis: Useful or harmful? Eur. J. Endocrinol. 2018, 178, D13–D25. [Google Scholar] [CrossRef] [PubMed]
- Eleni, A.; Panagiotis, P. A systematic review and meta-analysis of vitamin D and calcium in preventing osteoporotic fractures. Clin. Rheumatol. 2020, 39, 3571–3579. [Google Scholar] [CrossRef] [PubMed]
- Kahwati, L.C.; Weber, R.P.; Pan, H.; Gourlay, M.; LeBlanc, E.; Coker-Schwimmer, M.; Viswanathan, M. Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2018, 319, 1600–1612. [Google Scholar] [CrossRef]
- Zhao, J.-G.; Zeng, X.-T.; Wang, J.; Liu, L. Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis. JAMA 2017, 318, 2466–2482. [Google Scholar] [CrossRef]
- Bischoff-Ferrari, H.A.; Willett, W.C.; Wong, J.B.; Giovannucci, E.; Dietrich, T.; Dawson-Hughes, B. Fracture prevention with vitamin D supplementation: A meta-analysis of randomized controlled trials. JAMA 2005, 293, 2257–2264. [Google Scholar] [CrossRef]
- Kong, S.H.; Jang, H.N.; Kim, J.H.; Kim, S.W.; Shin, C.S. Effect of Vitamin D Supplementation on Risk of Fractures and Falls According to Dosage and Interval: A Meta-Analysis. Endocrinol. Metab. 2022, 37, 344–358. [Google Scholar] [CrossRef]
- Papadopoulou, S.K.; Papadimitriou, K.; Voulgaridou, G.; Georgaki, E.; Tsotidou, E.; Zantidou, O.; Papandreou, D. Exercise and Nutrition Impact on Osteoporosis and Sarcopenia—The Incidence of Osteosarcopenia: A Narrative Review. Nutrients 2021, 13, 4499. [Google Scholar] [CrossRef]
- Detopoulou, P.; Papadopoulou, S.K.; Voulgaridou, G.; Dedes, V.; Tsoumana, D.; Gioxari, A.; Gerostergios, G.; Detopoulou, M.; Panoutsopoulos, G.I. Ketogenic Diet and Vitamin D Metabolism: A Review of Evidence. Metabolites 2022, 12, 1288. [Google Scholar] [CrossRef]
- Detopoulou, P.; Tsiouda, T.; Pilikidou, M.; Palyvou, F.; Mantzorou, M.; Perzirkianidou, P.; Kyrka, K.; Methenitis, S.; Kondyli, F.S.; Voulgaridou, G.; et al. Dietary Habits Are Related to Phase Angle in Male Patients with Non-Small-Cell Lung Cancer. Curr. Oncol. 2022, 29, 8074–8083. [Google Scholar] [CrossRef]
- Kim, H.; Kim, B.-J.; Ahn, S.H.; Lee, S.H.; Koh, J.-M. Higher plasma platelet-activating factor levels are associated with increased risk of vertebral fracture and lower bone mineral density in postmenopausal women. J. Bone Min. Metab. 2015, 33, 701–707. [Google Scholar] [CrossRef]
- Detopoulou, P.; Fragopoulou, E.; Nomikos, T.; Yannakoulia, M.; Stamatakis, G.; Panagiotakos, D.B.; Antonopoulou, S. The relation of diet with PAF and its metabolic enzymes in healthy volunteers. Eur. J. Nutr. 2015, 54, 25–34. [Google Scholar] [CrossRef]
- Fragopoulou, E.; Detopoulou, P.; Alepoudea, E.; Nomikos, T.; Kalogeropoulos, N.; Antonopoulou, S. Associations between red blood cells fatty acids, desaturases indices and metabolism of platelet activating factor in healthy volunteers. Prostaglandins Leukot. Essent. Fat. Acids 2021, 164, 102234. [Google Scholar] [CrossRef]
- Argyrou, C.; Karlafti, E.; Lampropoulou-Adamidou, K.; Tournis, S.; Makris, K.; Trovas, G.; Dontas, I.; Triantafyllopoulos, I.K. Effect of calcium and vitamin D supplementation with and without collagen peptides on bone turnover in postmenopausal women with osteopenia. J. Musculoskelet Neuronal Interact. 2020, 20, 12–17. [Google Scholar]
- Kuchuk, N.O.; Pluijm, S.M.F.; van Schoor, N.M.; Looman, C.W.N.; Smit, J.H.; Lips, P. Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J. Clin. Endocrinol. Metab. 2009, 94, 1244–1250. [Google Scholar] [CrossRef]
- Seamans, K.M.; Hill, T.R.; Wallace, J.M.W.; Horigan, G.; Lucey, A.J.; Barnes, M.S.; Taylor, N.; Bonham, M.P.; Muldowney, S.; Duffy, E.M.; et al. Cholecalciferol supplementation throughout winter does not affect markers of bone turnover in healthy young and elderly adults. J. Nutr. 2010, 140, 454–460. [Google Scholar] [CrossRef]
- Wamberg, L.; Pedersen, S.B.; Richelsen, B.; Rejnmark, L. The effect of high-dose vitamin D supplementation on calciotropic hormones and bone mineral density in obese subjects with low levels of circulating 25-hydroxyvitamin d: Results from a randomized controlled study. Calcif. Tissue Int. 2013, 93, 69–77. [Google Scholar] [CrossRef]
- Peichl, P.; Griesmacherb, A.; Marteau, R.; Hejc, S.; Kumpan, W.; Müller, M.M.; Bröll, H. Serum crosslaps in comparison to serum osteocalcin and urinary bone resorption markers. Clin. Biochem. 2001, 34, 131–139. [Google Scholar] [CrossRef]
- Mukaiyama, K.; Kamimura, M.; Uchiyama, S.; Ikegami, S.; Nakamura, Y.; Kato, H. Elevation of serum alkaline phosphatase (ALP) level in postmenopausal women is caused by high bone turnover. Aging Clin. Exp. Res. 2015, 27, 413–418. [Google Scholar] [CrossRef]
- Kanazawa, I.; Yamaguchi, T.; Yamamoto, M.; Yamauchi, M.; Kurioka, S.; Yano, S.; Sugimoto, T. Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 2009, 94, 45–49. [Google Scholar] [CrossRef]
- Im, J.-A.; Yu, B.-P.; Jeon, J.Y.; Kim, S.-H. Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin. Chim. Acta 2008, 396, 66–69. [Google Scholar] [CrossRef] [PubMed]
- Sepulveda-Villegas, M.; Elizondo-Montemayor, L.; Trevino, V. Identification and analysis of 35 genes associated with vitamin D deficiency: A systematic review to identify genetic variants. J. Steroid Biochem. Mol. Biol. 2020, 196, 105516. [Google Scholar] [CrossRef] [PubMed]
- Rodopaios, N.E.; Petridou, A.; Mougios, V.; Koulouri, A.-A.; Vasara, E.; Papadopoulou, S.K.; Skepastianos, P.; Hassapidou, M.; Kafatos, A.G. Vitamin D status, vitamin D intake, and sunlight exposure in adults adhering or not to periodic religious fasting for decades. Int. J. Food Sci. Nutr. 2021, 72, 989–996. [Google Scholar] [CrossRef] [PubMed]
- Alathari, B.E.; Bodhini, D.; Jayashri, R.; Lakshmipriya, N.; Shanthi Rani, C.S.; Sudha, V.; Lovegrove, J.A.; Anjana, R.M.; Mohan, V.; Radha, V.; et al. A Nutrigenetic Approach to Investigate the Relationship between Metabolic Traits and Vitamin D Status in an Asian Indian Population. Nutrients 2020, 12, 1357. [Google Scholar] [CrossRef]
- Rodopaios, N.E.; Manolarakis, G.E.; Koulouri, A.-A.; Vasara, E.; Papadopoulou, S.K.; Skepastianos, P.; Dermitzakis, E.; Hassapidou, M.; Linardakis, M.K.; Kafatos, A.G. The significant effect on musculoskeletal metabolism and bone density of the Eastern Mediterranean Christian Orthodox Church fasting. Eur. J. Clin. Nutr. 2020, 74, 1736–1742. [Google Scholar] [CrossRef]
- Rodopaios, N.E.; Mougios, V.; Konstantinidou, A.; Iosifidis, S.; Koulouri, A.-A.; Vasara, E.; Papadopoulou, S.K.; Skepastianos, P.; Dermitzakis, E.; Hassapidou, M.; et al. Effect of periodic abstinence from dairy products for approximately half of the year on bone health in adults following the Christian Orthodox Church fasting rules for decades. Arch. Osteoporos. 2019, 14, 68. [Google Scholar] [CrossRef]
- Trivedi, D.P. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: Randomised double blind controlled trial. BMJ 2003, 326, 469. [Google Scholar] [CrossRef]
- Malihi, Z.; Wu, Z.; Stewart, A.W.; Lawes, C.M.; Scragg, R. Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: A systematic review and meta-analysis. Am. J. Clin. Nutr. 2016, 104, 1039–1051. [Google Scholar] [CrossRef]
- Autier, P.; Gandini, S.; Mullie, P. A Systematic Review: Influence of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Concentration. J. Clin. Endocrinol. Metab. 2012, 97, 2606–2613. [Google Scholar] [CrossRef]
- Mazidi, M.; Rezaie, P.; Vatanparast, H.; Kengne, A.P. Effect of statins on serum vitamin D concentrations: A systematic review and meta-analysis. Eur. J. Clin. Invest. 2017, 47, 93–101. [Google Scholar] [CrossRef]
- Siniscalchi, A.; Murphy, S.; Cione, E.; Piro, L.; Sarro, G.D.; Gallelli, L. Antiepileptic Drugs and Bone Health: Current Concepts. Psychopharmacol. Bull. 2020, 50, 36–44. [Google Scholar]
- Kupisz-Urbańska, M.; Płudowski, P.; Marcinowska-Suchowierska, E. Vitamin D Deficiency in Older Patients—Problems of Sarcopenia, Drug Interactions, Management in Deficiency. Nutrients 2021, 13, 1247. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Voulgaridou, G.; Papadopoulou, S.K.; Detopoulou, P.; Tsoumana, D.; Giaginis, C.; Kondyli, F.S.; Lymperaki, E.; Pritsa, A. Vitamin D and Calcium in Osteoporosis, and the Role of Bone Turnover Markers: A Narrative Review of Recent Data from RCTs. Diseases 2023, 11, 29. https://doi.org/10.3390/diseases11010029
Voulgaridou G, Papadopoulou SK, Detopoulou P, Tsoumana D, Giaginis C, Kondyli FS, Lymperaki E, Pritsa A. Vitamin D and Calcium in Osteoporosis, and the Role of Bone Turnover Markers: A Narrative Review of Recent Data from RCTs. Diseases. 2023; 11(1):29. https://doi.org/10.3390/diseases11010029
Chicago/Turabian StyleVoulgaridou, Gavriela, Sousana K. Papadopoulou, Paraskevi Detopoulou, Despoina Tsoumana, Constantinos Giaginis, Foivi S. Kondyli, Evgenia Lymperaki, and Agathi Pritsa. 2023. "Vitamin D and Calcium in Osteoporosis, and the Role of Bone Turnover Markers: A Narrative Review of Recent Data from RCTs" Diseases 11, no. 1: 29. https://doi.org/10.3390/diseases11010029