OBJECTIVE: To assess the decrease in serum calcitriol concentrations after hip fracture. METHODS: Serum concentrations of calcitriol, 25(OH)D, parathyroid hormone (PTH), directly measured free 25(OH)D, and indices of bone formation were measured in elderly patients with hip fracture (HF) and patients with elective hip replacement (EHR) at admission and after 7 weeks. RESULTS: A total of 45 patients with HF and 17 patients with EHR completed this prospective study. Baseline serum calcitriol levels were ≤ 60 pmol/l in 26% of the HF patients. After 7 weeks, they significantly decreased (p < 0.001). In patients with EHR, serum calcitriol was within the reference range in all but one patient and did not change during the 7-week recovery phase. Seven weeks after HF, a significant positive relationship was observed between the change in calcitriol and serum 25(OH)D concentration (r = 0.385, p = 0.009) and free 25(OH)D (r = 0.296, p = 0.048), and a decrease in calcitriol during recovery was associated with a decrease in serum PTH (p = 0.038). Seven weeks after HF, changes in both serum PTH and serum 25(OH)D concentrations contributed to the prediction of changes in serum calcitriol (R2 = 0.190, p = 0.012). CONCLUSIONS: Unlike patients with EHR, subjects with HF had low serum 25(OH)D and low free 25(OH)D concentrations at admission, while their serum 1,25D levels were relatively elevated. Decreases in circulating calcitriol levels in the 7 weeks following hip surgery were associated with a resolution of secondary hyperparathyroidism and low availability of free 25(OH)D.

Faculty of Medicine 1 Charles University Prague Czech Republic

Faculty of Medicine 3 Charles University Prague Czech Republic

Institute of Rheumatology Prague Czech Republic

Orthopedic Department Bulovka Hospital Prague Czech Republic

Zobrazit více v PubMed

Sahota O, Gaynor K, Harwood RH et al (2001) Hypovitaminosis D and ‘functional hypoparathyroidism’-the NoNoF (Nottingham Neck of Femur) study. Age Ageing 30:467–472 PubMed DOI

Sakuma M, Endo N, Oinuma T et al (2006) Vitamin D and intact PTH status in patients with hip fracture. Osteoporos Int 17:1608–1614 PubMed DOI

Fisher AA, Davis MW (2007) Calcium-PTH-vitamin D axis in older patients with hip fracture. Osteoporos Int 18:693–695; author reply 697.

Wang N, Chen Y, Ji J et al (2020) The relationship between serum vitamin D and fracture risk in the elderly: a meta-analysis. J Orthop Surg Res 15:81 PubMed DOI PMC

Zhuang HF, Wang PW, Li YZ et al (2020) Analysis of related factors of brittle hip fracture in postmenopausal women with osteoporosis. Orthop Surgery 12:194–198 DOI

Nielson CM, Jones KS, Bouillon R et al (2016) Role of assay type in determining free 25-hydroxyvitamin D levels in diverse populations. N Engl J Med 374:1695–1696 PubMed DOI PMC

Schwartz JB, Gallagher JC, Jorde R et al (2018) Determination of free 25(OH)D concentrations and their relationships to total 25(OH)D in multiple clinical populations. J Clin Endocrinol Metab 103:3278–3288 PubMed DOI PMC

Xie Z, Wang X, Bikle DD (2020) Editorial: vitamin D binding protein, total and free vitamin D levels in different physiological and pathophysiological conditions. Frontiers in endocrinology 11.

Wang X, Meng L, Su C et al (2020) Low free (but not total) 25-hydroxyvitamin D levels in subjects with normocalcemic hyperparathyroidism. Endocr Pract 26:174–178 PubMed DOI

Briggs AD, Kuan V, Greiller CL et al (2013) Longitudinal study of vitamin D metabolites after long bone fracture. J Bone Miner Res 28:1301–1307 PubMed DOI

Meller Y, Kestenbaum RS, Shany S et al (1985) Parathormone, calcitonin, and vitamin D metabolites during normal fracture healing in geriatric patients. Clin Orthop Relat Res:272–279.

Yu-Yahiro JA, Michael RH, Dubin NH et al (2001) Serum and urine markers of bone metabolism during the year after hip fracture. J Am Geriatr Soc 49:877–883 PubMed DOI

St-Arnaud R, Naja RP (2011) Vitamin D metabolism, cartilage and bone fracture repair. Mol Cell Endocrinol 347:48–54 PubMed DOI

Kato A, Bishop JE, Norman AW (1998) Evidence for a 1 alpha,25-dihydroxyvitamin D3 receptor/binding protein in a membrane fraction isolated from a chick tibial fracture-healing callus. Biochem Biophys Res Commun 244:724–727 PubMed DOI

Lidor C, Dekel S, Edelstein S (1987) The metabolism of vitamin D3 during fracture healing in chicks. Endocrinology 120:389–393 PubMed DOI

Jingushi S, Iwaki A, Higuchi O et al (1998) Serum 1alpha, 25-dihydroxyvitamin D3 accumulates into the fracture callus during rat femoral fracture healing. Endocrinology 139:1467–1473 PubMed DOI

Meller Y, Kestenbaum RS, Mozes M et al (1984) Mineral and endocrine metabolism during fracture healing in dogs. Clin Orthop Relat Res 187:289–295

Cappola AR, Hawkes WG, Blocher N et al (2011) The hormonal profile of hip fracture female patients differs from community-dwelling peers over a 1-year follow-up period. Osteoporos Int 22:339–344 PubMed DOI

Benhamou CL, Tourliere D, Gauvain JB et al (1995) Calciotropic hormones in elderly people with and without hip fracture. Osteoporos Int 5:103–107 PubMed DOI

Boonen S, Broos P, Verbeke G et al (1997) Calciotropic hormones and markers of bone remodeling in age-related (type II) femoral neck osteoporosis: alterations consistent with secondary hyperparathyroidism-induced bone resorption. J Gerontol A Biol Sci Med Sci 52:M286-293 PubMed DOI

Rosen C, Donahue LR, Hunter S et al (1992) The 24/25-kDa serum insulin-like growth factor-binding protein is increased in elderly women with hip and spine fractures. J Clin Endocrinol Metab 74:24–27 PubMed

LeBoff MS, Kohlmeier L, Hurwitz S et al (1999) Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA 281:1505–1511 PubMed DOI

Maruyama M, Rhee C, Utsunomiya T et al (2020) Modulation of the inflammatory response and bone healing. Frontiers in Endocrinology 11.

Visser E, de Roos NM, Oosting E et al (2018) Association between preoperative vitamin D status and short-term physical performance after total hip arthroplasty: a prospective study. Ann Nutr Metab 73:252–260 PubMed DOI

Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501 PubMed DOI

Need AG, O’Loughlin PD, Morris HA et al (2008) Vitamin D metabolites and calcium absorption in severe vitamin D deficiency. J Bone Miner Res 23:1859–1863 PubMed DOI

Vieth R, Ladak Y, Walfish PG (2003) Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. J Clin Endocrinol Metab 88:185–191 PubMed DOI

Reusch J, Ackermann H, Badenhoop K (2009) Cyclic changes of vitamin D and PTH are primarily regulated by solar radiation: 5-year analysis of a German (50 degrees N) population. Horm Metab Res 41:402–407 PubMed DOI

Holvik K, Meyer HE, Sogaard AJ et al (2006) Biochemical markers of bone turnover and their relation to forearm bone mineral density in persons of Pakistani and Norwegian background living in Oslo, Norway: the Oslo Health Study. Eur J Endocrinol 155:693–699 PubMed DOI

Christensen MH, Lien EA, Hustad S et al (2010) Seasonal and age-related differences in serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone in patients from Western Norway. Scand J Clin Lab Invest 70:281–286 PubMed DOI

Johansen A, Stone MD, O’Mahony MS et al (1997) Reliability of parathyroid hormone measurements in the period immediately following hip fracture. Age Ageing 26:175–178 PubMed DOI

Ng K, St John A, Bruce DG (1994) Secondary hyperparathyroidism, vitamin D deficiency and hip fracture: importance of sampling times after fracture. Bone Miner 25:103–109 PubMed DOI

Sato Y, Kaji M, Higuchi F et al (2001) Changes in bone and calcium metabolism following hip fracture in elderly patients. Osteoporos Int 12:445–449 PubMed DOI

Dubin NH, Monahan LK, Yu-Yahiro JA et al (1999) Serum concentrations of steroids, parathyroid hormone, and calcitonin in postmenopausal women during the year following hip fracture: effect of location of fracture and age. J Gerontol A Biol Sci Med Sci 54:M467-473 PubMed DOI

Walker AT, Stewart AF, Korn EA et al (1990) Effect of parathyroid hormone-like peptides on 25-hydroxyvitamin D-1 alpha-hydroxylase activity in rodents. Am J Physiol 258:E297-303 PubMed

Cosman F, Dawson-Hughes B, Wan X et al (2012) Changes in vitamin D metabolites during teriparatide treatment. Bone 50:1368–1371 PubMed DOI

Minisola S, Marin F, Kendler DL et al (2019) Serum 25-hydroxy-vitamin D and the risk of fractures in the teriparatide versus risedronate VERO clinical trial. Arch Osteoporos 14:10 PubMed DOI

Bischoff H, Stahelin HB, Vogt P et al (1999) Immobility as a major cause of bone remodeling in residents of a long-stay geriatric ward. Calcif Tissue Int 64:485–489 PubMed DOI

Theiler R, Stahelin HB, Tyndall A et al (1999) Calcidiol, calcitriol and parathyroid hormone serum concentrations in institutionalized and ambulatory elderly in Switzerland. Int J Vitam Nutr Res 69:96–105 PubMed DOI

Kolek OI, Hines ER, Jones MD et al (2005) 1alpha,25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol 289:G1036–G1042 PubMed DOI

Alshayeb H, Showkat A, Wall BM et al (2014) Activation of FGF-23 mediated vitamin D degradative pathways by cholecalciferol. J Clin Endocrinol Metab 99:E1830-1837 PubMed DOI PMC

Alkalay D, Shany S, Dekel S (1989) Serum and bone vitamin D metabolites in elective patients and patients after fracture. J Bone Joint Surg Br 71:85–87 PubMed DOI

Resmini G, Migliaccio S, Dalle Carbonare L et al (2011) Differential characteristics of bone quality and bone turnover biochemical markers in patients with hip fragility fractures and hip osteoarthritis: results of a clinical pilot study. Aging Clin Exp Res 23:99–105 PubMed DOI

Norman AW, Okamura WH, Bishop JE et al (2002) Update on biological actions of 1alpha,25(OH)2-vitamin D3 (rapid effects) and 24R, 25(OH)2-vitamin D3. Mol Cell Endocrinol 197:1–13 PubMed DOI

Dirks NF, Ackermans MT, Lips P et al (2018) The when, what and how of measuring vitamin D metabolism in clinical medicine. Nutrients 10.

MacLaughlin J, Holick MF (1985) Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 76:1536–1538 PubMed DOI PMC

Vaculik J, Stepan JJ, Dungl P et al (2017) Secondary fracture prevention in hip fracture patients requires cooperation from general practitioners. Arch Osteoporos 12:49 PubMed DOI

Dekel S, Salama R, Edelstein S (1983) The effect of vitamin D and its metabolites on fracture repair in chicks. Clin Sci (Lond) 65:429–436 DOI

Glendenning P, Chew GT, Seymour HM et al (2009) Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone 45:870–875 PubMed DOI

Schwartz JB, Kane L, Bikle D (2016) Response of vitamin D concentration to vitamin D3 administration in older adults without sun exposure: a randomized double-blind trial. J Am Geriatr Soc 64:65–72 PubMed DOI PMC

Trummer C, Schwetz V, Pandis M et al (2017) Effects of vitamin D supplementation on IGF-1 and calcitriol: a randomized-controlled trial. Nutrients 9.

Zittermann A, Ernst JB, Prokop S, Fuchs U, Dreier J, Kuhn J, Berthold HK, Pilz S, Gouni-Berthold I, Gummert JF (2018) Vitamin D supplementation and bone turnover in advanced heart failure: the EVITA trial. Osteoporos Int 29:579–586 PubMed DOI

A decrease in serum 1,25(OH)2D after elective hip replacement and during bone healing is associated with changes in serum iron and plasma FGF23