Abstract
OBJECTIVE
Hip-fracture patients with vitamin D deficiency can have either secondary hyperparathyroidism or normal levels of parathyroid hormone (PTH). We hypothesized that bone mineral density (BMD) could be lower in patients with high PTH levels than in those with normal levels of PTH, irrespectively of the severity of vitamin D depletion.
DESIGN
In this cross-sectional study, we examined 405 women who had serum 25-hydroxyvitamin D below 12ng/ml 20.0 ± 5.9 (mean ± SD) days after a hip-fracture. PTH was assessed by a chemiluminescent immunometric assay and BMD by dual-energy x-ray absorptiometry at the unfractured femoral neck.
RESULTS
BMD was significantly lower in the 148 women with secondary hyperparathyroidism than in the 257 with normal PTH levels: the mean T-score (SD) was −2.88 (0.93) and −2.65 (0.83), respectively, in the two groups (mean difference 0.23; 95% CI 0.05–0.41; P = 0.010). The association between PTH status and BMD persisted after adjustment for age, body mass index, phosphate, albumin-adjusted total calcium, 25-hydroxyvitamin D, estimated glomerular filtration rate, and magnesium (P=0.01). The presence of secondary hyperparathyroidism was significantly associated with a femoral neck T-score lower than −2.5. The adjusted odds ratio was 1.81 (95% CI 1.11–2.95; P=0.017).
CONCLUSIONS
Our results show that PTH levels in the presence of severe vitamin D deficiency were significantly associated with femoral BMD in women with hip-fracture. Prevention and treatment of vitamin D deficiency may be particularly relevant in women who develop secondary hyperparathyroidism.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Lieben L, Carmeliet G, Masuyama R, 2011 Calcemic actions of vitamin D: effects on the intestine, kidney and bone. Best Pract Res Clin Endocrinol Metab 25: 561–572.
Marcelli C, Chavoix C, Dargent-Molina P, 2015 Beneficial effects of vitamin D on falls and fractures: is cognition rather than bone or muscle behind these benefits? Osteoporosis Int 26: 1–10.
Iolascon G, de Sire A, Calafiore D, Moretti A, Gimigliano R, Gimigliano F, 2015 Hypovitaminosis D is associated with a reduction in upper and lower limb muscle strength and physical performance in post-menopausal women: a retrospective study. Aging Clin Exp Res 27: Suppl 1: 23–30.
Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), 2013 European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24: 23–57.
Van Schoor NM, Lips P, 2011 Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab 25: 671–680.
Katrinaki M, Kampa M, Margioris A, Castanas E, Malliaraki N, 2016 Vitamin D levels in a large Mediterranean cohort: reconsidering normal cut-off values. Hormones 15: 205–223.
Di Monaco M, Castiglioni C, Vallero F, Di Monaco R, Tappero R, 2011 Appendicular lean mass does not mediate the significant association between vitamin D status and functional outcome in hip fracture women. Arch Phys Med Rehabil 92: 271–276.
LeBoff MS, Hawkes WG, Glowacki J, Yu-Yahiro J, Hurwitz S, Magaziner J, 2008 Vitamin D-deficiency and post-fracture changes in lower extremity function and falls in women with hip fractures. Osteoporos Int 19: 1283–1290.
Bischoff-Ferrari HA, Can U, Staehelin HB, et al, 2008 Severe vitamin D deficiency in Swiss hip fracture patients. Bone 42: 597–602.
Ramason R, Selvaganapathi N, Ismail NH, Wong WC, Rajamoney GN, Chong MS, 2014 Prevalence of vitamin d deficiency in patients with hip fracture seen in an orthogeriatric service in sunny Singapore. Geriatr Orthop Surg Rehabil 5: 82–86.
Di Monaco M, Castiglioni C, Di Monaco R, Tappero R, 2016 Time trend 2000–2013 of vitamin D status in older people who sustain hip fractures: steps forward or steps back? A retrospective study of 1599 inpatients. Eur J Phys Rehabil Med 52: 502–507.
Von Mühlen DG, Greendale GA, Garland CF, Wan L, Barrett-Connor E, 2005 Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: the Rancho Bernardo Study. Osteoporos Int 16: 1721–1726.
Stein MS, Wark JD, Scherer SC, et al, 1999 Falls relate to vitamin D and parathyroid hormone in an Australian nursing home and hostel. J Am Geriatr Soc 47: 1195–1201.
Singhellakis PN, Malandrinou FC, Psarrou CJ, Danelli AM, Tsalavoutas SD, Constandellou ES, 2011 Vitamin D deficiency in white, apparently healthy, free-living adults in a temperate region. Hormones (Athens) 10: 131–143.
Lips P, 2001 Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocrine Rev 22: 477–501.
Sahota O, Gaynor K, Harwood RH, Hosking DJ, 2001 Hypovitaminosis D and ‘functional hypoparathyroidism’-the NoNoF (Nottingham Neck of Femur) study. Age Ageing 30: 467–472.
Bjorkman MP, Sorva AJ, Risteli J, Tilvis RS, 2009 Low parathyroid hormone levels in bedridden geriatric patients with vitamin D deficiency. J Am Geriatr Soc 57: 1045–1050.
Amouzougan A, Chopin F, Laporte S, Vico L, Thomas T, 2011 Functional hypoparathyroidism in postmenopausal women with fragility fracture. Joint Bone Spine 79: 170–175.
Fisher A, Srikusalanukul W, Davis M, Smith P, 2010 Hip fracture type: important role of parathyroid hormone (PTH) response to hypovitaminosis D. Bone 47: 400–407.
Di Monaco M, Castiglioni C, Vallero F, Di Monaco R, Tappero R, 2013 Parathyroid hormone response to severe vitamin D deficiency is sex associated: an observational study of 571 hip fracture inpatients. J Nutr Health Aging 17: 180–184.
Di Monaco M, Castiglioni C, Vallero F, Di Monaco R, Tappero R, 2014 Parathyroid hormone variance is marginally explained by a panel of determinants: a cross sectional study of 909 hip-fracture patients. J Bone Miner Metab 32: 573–579.
Pioli G, Barone A, Mussi C et al; GIOG, 2014 The management of hip fracture in the older population. Joint position statement by Gruppo Italiano Ortogeriatria (GIOG). Aging Clin Exp Res 26: 547–553.
Di Monaco M, Vallero F, De Toma E et al, 2012 Adherence to recommendations for fall prevention significantly affects the risk of falling after hip fracture: post-hoc analyses of a quasi-randomized controlled trial. Eur J Phys Rehabil Med 48: 9–15.
Sosa M, Saavedra P, Gomez-de-Tejada MJ, et al, 2015 High prevalence of undiagnosed vertebral fractures in patients suffering from hip fracture at their hospital admission: weak concordance among observers. Aging Clin Exp Res 27: 835–839.
Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C, 2009 Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int 20: 1633–1650.
Fisher A, Goh S, Srikusalanukul W, Davis M, 2009 Elevated serum PTH is independently associated with poor outcomes in older patients with hip fracture and vitamin D inadequacy. Calcif Tissue Int 85: 301–309.
Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A, 2006 25-hydroxyvitamin D, parathyroid hormone, and functional recovery after hip fracture in elderly patients. J Bone Miner Metab 24: 42–47.
Fisher AA, Southcott EK, Srikusalanukul W, et al, 2007 Relationships between myocardial injury, all-cause mortality, vitamin D, PTH, and biochemical bone turnover markers in older patients with hip fractures. Ann Clin Lab Sci 37: 222–232.
Madsen CM, Jorgensen HL, Lind B, et al, 2012 Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice. Injury 43: 1052–1057.
Bjorkman MP, Sorva AJ, Tilvis RS, 2008 Elevated serum parathyroid hormone predicts impaired survival prognosis in a general aged population. Eur J Endocrinol 158: 749–753.
Domiciano DS, Machado LG, Lopes JB, et al, 2016 Bone mineral density and parathyroid hormone as Independent risk factors for mortality in community-dwelling older adults: A population-based prospective cohort study in Brazil. The São Paulo Ageing & Health (spah) study. J Bone Miner Res 31: 1146–1157.
de Souza Genaro P, de Medeiros Pinheiro M, Szejnfeld VL, Martini LA, 2015 Secondary hyperparathyroidism and its relationship with sarcopenia in elderly women. Arch Gerontol Geriatr 60: 349–353.
Di Monaco M, Castiglioni C, De Toma E, et al, 2015 Presarcopenia and sarcopenia in hip-fracture women: prevalence and association with ability to function in activities of daily living. Aging Clin Exp Res 27: 465–472.
Rude RK, Singer FR, Gruber HE, 2009 Skeletal and hormonal effects of magnesium deficiency. J Am Coll Nutr 28: 131–141.
Sahota O, Mundey MK, San P, Godber IM, Hosking DJ, 2006 Vitamin D insufficiency and the blunted PTH response in established osteoporosis: the role of magnesium deficiency. Osteoporos Int 17: 1013–1021.
Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T, 2011 Acute-onset hypomagnesemia-induced hypocalcemia caused by refractoriness of bones and renal tubules to parathyroid hormone. J Bone Miner Metab 29: 752–755.
Zaloga GP, 1989 Interpretation of the serum Mg level. Chest 95: 257–258.
Sahota O, Mundey MK, San P, Godber IM, Lawson N, Hosking DJ, 2004 The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone 35: 312–319.
Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M, 2014 Vitamin D and DBP: the free hormone hypothesis revisited. J Steroid Biochem Mol Biol 144: 132–137.
Powe CE, Evans MK, Wenger J, et al, 2013 Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 369: 1991–2000.
Koren-Hakim T, Weiss A, Hershkovitz A, et al, 2012 The relationship between nutritional status of hip fracture operated elderly patients and their functioning, comorbidity and outcome. Clin Nutr 31: 917–921.
Meier U, Gressner O, Lammert F, Gressner AM, 2006 Gc-globulin: roles in response to injury. Clin Chem 52: 1247–1253.
Binkley N, Wiebe D, 2013 Clinical controversies in vitamin D: 25(OH)D measurement, target concentration, and supplementation. J Clin Densitom 16: 402–408.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Di Monaco, M., Castiglioni, C. & Tappero, R. Parathyroid hormone response to severe vitamin D deficiency is associated with femoral neck bone mineral density: an observational study of 405 women with hip-fracture. Hormones 15, 527–533 (2016). https://doi.org/10.14310/horm.2002.1709
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.14310/horm.2002.1709