A pilot study of change in fracture risk in patients with acute respiratory distress syndrome

Jaikitry Rawal, Mark J W McPhail, Gamumu Ratnayake, Pearl Chan, John Moxham, Stephen D R Harridge, Nicholas Hart, Hugh E Montgomery, Zudin A Puthucheary, Jaikitry Rawal, Mark J W McPhail, Gamumu Ratnayake, Pearl Chan, John Moxham, Stephen D R Harridge, Nicholas Hart, Hugh E Montgomery, Zudin A Puthucheary

Abstract

Introduction: Acute skeletal muscle wasting is a major contributor to post critical illness physical impairment. However, the bone response remains uncharacterized. We prospectively investigated the early changes in bone mineral density (BMD) and fracture risk in critical illness.

Methods: Patients were prospectively recruited ≤24 hours following intensive care unit (ICU) admission to a university teaching or a community hospital (August 2009 to April 2011). All were aged >18 years and expected to be intubated for >48 hours, spend >7 days in critical care and survive ICU admission. Forty-six patients were studied (55.3% male), with a mean age of 54.4 years (95% confidence interval (CI): 49.1 to 59.6) and an APACHE II score of 23.9 (95% CI: 22.4 to 25.5). Calcaneal dual X-ray absorptiometry (DXA) assessment of BMD was performed on day 1 and 10. Increase in fracture risk was calculated from the change in T-score.

Results: BMD did not change between day 1 and 10 in the cohort overall (0.434 (95% CI: 0.405 to 0.463) versus 0.425 g/cm(2) (95% CI: 0.399 to 0.450), P = 0.58). Multivariable logistical regression revealed admission corrected calcium (odds ratio (OR): 1.980 (95% CI: 1.089 to 3.609), P = 0.026) and admission PaO2-to-FiO2 ratio (OR: 0.916 (95% CI: 0.833 to 0.998), P = 0.044) to be associated with >2% loss of BMD. Patients with acute respiratory distress syndrome had a greater loss in BMD than those without (-2.81% (95% CI: -5.73 to 0.118%), n = 34 versus 2.40% (95% CI: 0.204 to 4.586%), n = 12, P = 0.029). In the 34 patients with acute respiratory distress syndrome, fracture risk increased by 19.4% (95% CI: 13.9 to 25.0%).

Conclusions: Patients with acute respiratory distress syndrome demonstrated early and rapid bone demineralisation with associated increase in fracture risk.

Figures

Figure 1
Figure 1
Change in T-score and percentage increase in fracture risk in patients with (n = 34) and without (n = 12) acute respiratory distress syndrome. FiO2 = Fraction of inspired oxygen, PaO2 = Partial pressure of oxygen in blood. Mann-Whitney U test was performed between groups, *P <0.05.

References

    1. Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364:1293–1304. doi: 10.1056/NEJMoa1011802.
    1. Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348:683–693. doi: 10.1056/NEJMoa022450.
    1. Iwashyna TJ. Survivorship will be the defining challenge of critical care in the 21st century. Ann Intern Med. 2010;153:204–205. doi: 10.7326/0003-4819-153-3-201008030-00013.
    1. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310:1591–1600. doi: 10.1001/jama.2013.278481.
    1. Chen JH, Liu C, You L, Simmons CA. Boning up on Wolff’s Law: mechanical regulation of the cells that make and maintain bone. J Biomech. 2010;43:108–118. doi: 10.1016/j.jbiomech.2009.09.016.
    1. Lang TF. The bone-muscle relationship in men and women. J Osteoporos. 2011;2011:702735.
    1. Schoenau E. From mechanostat theory to development of the “Functional Muscle-Bone-Unit”. J Musculoskelet Neuronal Interact. 2005;5:232–238.
    1. Krolner B, Toft B. Vertebral bone loss: an unheeded side effect of therapeutic bed rest. Clin Sci (Lond). 1983;64:537–540.
    1. Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR. Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature. 1986;319:516–518. doi: 10.1038/319516a0.
    1. Bushinsky DA, Smith SB, Gavrilov KL, Gavrilov LF, Li J, Levi-Setti R. Acute acidosis-induced alteration in bone bicarbonate and phosphate. Am J Physiol Renal Physiol. 2002;283:F1091–F1097. doi: 10.1152/ajprenal.00155.2002.
    1. Van den Berghe G, Van Roosbroeck D, Vanhove P, Wouters PJ, De Pourcq L, Bouillon R. Bone turnover in prolonged critical illness: effect of vitamin D. J Clin Endocrinol Metab. 2003;88:4623–4632. doi: 10.1210/jc.2003-030358.
    1. Dubois EF, Roder E, Dekhuijzen PN, Zwinderman AE, Schweitzer DH. Dual energy X-ray absorptiometry outcomes in male COPD patients after treatment with different glucocorticoid regimens. Chest. 2002;121:1456–1463. doi: 10.1378/chest.121.5.1456.
    1. Uzkeser H, Yildirim K, Aktan B, Karatay S, Kaynar H, Araz O, et al. Bone mineral density in patients with obstructive sleep apnea syndrome. Sleep Breath. 2013;17:339–342. doi: 10.1007/s11325-012-0698-y.
    1. Smith LM, Cuthbertson B, Harvie J, Webster N, Robins S, Ralston SH. Increased bone resorption in the critically ill: association with sepsis and increased nitric oxide production. Crit Care Med. 2002;30:837–840. doi: 10.1097/00003246-200204000-00020.
    1. Orford NR, Saunders K, Merriman E, Henry M, Pasco J, Stow P, et al. Skeletal morbidity among survivors of critical illness. Crit Care Med. 2011;39:1295–1300. doi: 10.1097/CCM.0b013e318211ff3d.
    1. Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA. 2002;288:1889–1897. doi: 10.1001/jama.288.15.1889.
    1. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526–2533.
    1. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A. Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res. 2004;19:1006–1012. doi: 10.1359/JBMR.040307.
    1. Goodman RB, Pugin J, Lee JS, Matthay MA. Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev. 2003;14:523–535. doi: 10.1016/S1359-6101(03)00059-5.
    1. Ding C, Parameswaran V, Udayan R, Burgess J, Jones G. Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab. 2008;93:1952–1958. doi: 10.1210/jc.2007-2325.
    1. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337–342. doi: 10.1038/nature01658.
    1. Bendre MS, Montague DC, Peery T, Akel NS, Gaddy D, Suva LJ. Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone. 2003;33:28–37. doi: 10.1016/S8756-3282(03)00086-3.
    1. Lieben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baatsen P, et al. Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. J Clin Invest. 2012;122:1803–1815. doi: 10.1172/JCI45890.
    1. Bagshaw SM, Stelfox HT, McDermid RC, Rolfson DB, Tsuyuki RT, Baig N, et al. Association between frailty and short- and long-term outcomes among critically ill patients: a multicentre prospective cohort study. CMAJ. 2014;186:E95–E102. doi: 10.1503/cmaj.130639.
    1. Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369:1306–1316. doi: 10.1056/NEJMoa1301372.
    1. Zhang B, Cory E, Bhattacharya R, Sah R, Hargens AR. Fifteen days of microgravity causes growth in calvaria of mice. Bone. 2013;56:290–295. doi: 10.1016/j.bone.2013.06.009.
    1. Sun LW, Luan HQ, Huang YF, Wang Y, Fan YB. Effects of local vibration on bone loss in -tail-suspended rats. Int J Sports Med. 2014;35:615–624. doi: 10.1055/s-0033-1358468.
    1. Sherk VD, Chrisman C, Smith J, Young KC, Singh H, Bemben MG, et al. Acute bone marker responses to whole-body vibration and resistance exercise in young women. J Clin Densitom. 2013;16:104–109. doi: 10.1016/j.jocd.2012.07.009.
    1. Nicolaije C, Koedam M, van Leeuwen JP. Decreased oxygen tension lowers reactive oxygen species and apoptosis and inhibits osteoblast matrix mineralization through changes in early osteoblast differentiation. J Cell Physiol. 2012;227:1309–1318. doi: 10.1002/jcp.22841.
    1. Dandajena TC, Ihnat MA, Disch B, Thorpe J, Currier GF. Hypoxia triggers a HIF-mediated differentiation of peripheral blood mononuclear cells into osteoclasts. Orthod Craniofac Res. 2012;15:1–9. doi: 10.1111/j.1601-6343.2011.01530.x.
    1. Muschitz C, Dimai HP, Kocijan R, Kaider A, Zendeli A, Kuhne F, et al. The discriminatory capacity of BMD measurements by DXA and dual X-ray and laser (DXL) at the calcaneus including clinical risk factors for detecting patients with vertebral fractures. Osteoporos Int. 2013;24:2181–2190. doi: 10.1007/s00198-013-2266-0.

Source: PubMed

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