ORIGINAL ARTICLE
Effectiveness of Vitamin D Therapy in Orthopaedic Trauma Patients Daniel S. Robertson, MD,* Tyler Jenkins, MD,† Yvonne M. Murtha, MD,‡ Gregory J. Della Rocca, MD, PhD,‡ David A. Volgas, MD,‡ James P. Stannard, MD,‡ and Brett D. Crist, MD‡
Objective: The purpose of this study was to determine the
Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
effectiveness of our vitamin D treatment protocol in managing low serum vitamin D levels in orthopaedic trauma patients.
(J Orthop Trauma 2015;29:e451–e453)
Methods: A retrospective review was conducted of all orthopaedic trauma patients at a university level I trauma center over 20 months. Patients were included if they had an initial and repeat 25-hydroxy (OH) vitamin D serum level available. Vitamin D deficiency was defined as serum 25-hydroxy vitamin D level with less than 20 ng/mL. Vitamin D insufficiency was defined as serum 25-hydroxy vitamin D level between 20 and 32 ng/mL. The standard regimen for all patients was over-the-counter vitamin D3 1000 IU and 1500 mg of calcium daily. Patients with vitamin D deficiency or insufficiency also received 50,000 IU of ergocalciferol (D2) weekly until their 25-hydroxyvitamin D level normalized or their fracture healed. No compliance monitoring was performed except for questioning at each clinic visit.
Results: A total of 201 patients met the inclusion criteria. Thirtytwo patients had a normal initial 25-hydroxyvitamin D level, and 84% maintained their normal level, whereas 16% became insufficient or deficient. There were 88 patients insufficient initially and 54.5% improved to normal and 8% became deficient. In the vitamin D deficiency group (81), 26% remained deficient and 74% improved to insufficient. The average increase in serum 25-OH vitamin D with treatment (in nanograms per milliliter) was statistically significant for both the insufficient and deficient groups.
Conclusions: Vitamin D therapy improved the majority of the patients’ vitamin D-25-OH level but did not normalize most. Patients with initial deficiency had the largest improvement. This study indicates that vigilance is required to adequately treat a low serum vitamin D-25-OH level. Key Words: vitamin D deficiency, musculoskeletal trauma, fracture healing Accepted for publication June 1, 2015. From the *Department of Orthopaedics, University of Texas Health Science Center at San Antonio, San Antonio, TX; †Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL; and ‡Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, MO. Presented at the Orthopaedic Trauma Association, Annual Meeting, October 12, 2013, Phoenix, AZ. The authors report no conflict of interest. Reprints: Brett D. Crist, MD, Department of Orthopaedic Surgery, University of Missouri, One Hospital Drive, N119, Columbia, MO 65212 (e-mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Orthop Trauma Volume 29, Number 11, November 2015
INTRODUCTION Vitamin D is an important prohormone in the regulation and maintenance of numerous physiologic systems in the human. It plays a role in cardiac, immune, digestive systems, and the musculoskeletal system.1,2 Low vitamin D levels are associated with a higher incidence of fracture in the elderly3 and recalcitrant tibial nonunions.4 At our institution, we reviewed our orthopaedic trauma patients with fractures who had serum 25-hydroxy (25-OH) vitamin levels available over a 20-month period. Records for 889 patients were reviewed, and 77% of them had either 25OH vitamin D deficiency or insufficiency, as defined by Hollis.5,6 During this review period, it was noted that a significant number of patients had a low serum 25-OH vitamin D level. Based on these findings and its potential implications in patient outcomes, our center implemented a protocol-driven effort to supplement patients during the fracture healing period. The purpose of this study was to evaluate the effectiveness of our vitamin D treatment protocol in orthopaedic trauma patients. Our hypothesis was that vitamin D therapy normalized serum 25-OH vitamin D levels.
PATIENTS AND METHODS After institutional review board approval, a retrospective review was performed for all orthopaedic trauma patients with a fracture at our American College of Surgeons verified level I university trauma center from January 1, 2009 to September 30, 2010. Patient inclusion criteria were they had to be at least 18 years old, they had a fracture managed by one of 4 attending orthopaedic trauma surgeons, and they had an available serum 25-OH vitamin D level available within 2 weeks from their injury and a repeat 25-OH vitamin D level available. The 25-OH form of vitamin D is the inactive serum form but is found to be the most accurate measure of systemic vitamin D levels.7 During the review period when serum vitamin D levels were obtained, the standard regimen for all patients was over-the-counter vitamin D3 1000 IU and 1500 mg of calcium daily. Patients with serum 25-OH vitamin D deficiency or insufficiency8 also received an 8-week prescription www.jorthotrauma.com |
e451
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Robertson et al
J Orthop Trauma Volume 29, Number 11, November 2015
for weekly 50,000 IU ergocalciferol (D2) until their 25-OH vitamin D level normalized or their fracture healed, which correlated with the risk assessment performed by Hathcock et al.9 No complications were noted. Patients with either a history of hypercalcemia or at risk for hypercalcemia—noted as calcium levels higher than 10.5 mg/dL—were excluded from this regimen. Standard clinic follow-up was performed at 2-, 6-, and 12-week visits and then every 2–3 months until fracture healing occurred. Follow-up serum 25-OH vitamin D levels were encouraged after the 8-week course of ergocalciferol, per our protocol. No compliance monitoring was performed except for questioning at each clinic visit. We gave calcium and vitamin D supplementation prescriptions when patients left the hospital and on follow-up verified that these were on their medication lists. We then provided patients information on over-the-counter calcium and vitamin D supplements and the required amounts they needed to take.
the insufficient group improved to normal, and 7 patients (8%) became deficient. The remaining 33 patients (37.5%) remained insufficient. The average change for the insufficient group was an increase of 8.79 ng/mL with treatment and was statistically significant (P , 0.05). Of the 81 patients with 25OH vitamin D deficiency, 26% (21) remained deficient and 74% (60) improved to the insufficient level. The deficient group had the largest average increase of 14.93 ng/mL and was also statistically significant (P , 0.05). Follow-up values were determined after 8 weeks of therapy.
Statistical Methods Descriptive statistics including the mean, median, and mode were calculated. A x2 test was performed if all cell frequencies were greater than 5. The Fisher exact probability test was used if any of the cell frequencies were 5 or less. We performed 1-sample T tests to calculate significant change in values. P values ,0.05 were considered statistically significant.
Definitions Vitamin D deficiency was defined as serum 25-hydroxy vitamin D level with less than 20 ng/mL. Vitamin D insufficiency was defined as serum 25-hydroxy vitamin D level between 20 and 32 ng/mL.8 By comparison, the Institute of Medicine and the Endocrine Society define deficiency as less than 20 ng/mL and between 21–29 ng/mL, respectively.10
RESULTS Two hundred one patients had initial and repeat serum 25-OH vitamin D levels. Of the 32 patients with a normal initial 25-OH vitamin D level, 84% (27) remained normal and 16% (5) became insufficient or deficient during clinical follow-up (Table 1). The average change in 25-OH vitamin D levels for this subgroup was an increase of 1.9 ng/mL and was not statistically significant (P = 0.17). The insufficient group consisted of 88 patients. Forty-eight patients (54.5%) in
TABLE 1. Initial Serum 25-OH Vitamin D Levels for Each Patient Group, Follow-up Vitamin D Levels, and Average Change
Vitamin D-25-OH Level Normal ($32 ng/mL) Insufficiency (,32 ng/mL) Deficiency (,20 ng/mL)
Average Initial Vitamin D-25 Level, ng/mL
Average Repeat Vitamin D-25 Level, ng/mL
Average Increase in Vitamin D-25 Level, ng/mL
39.13 25.19 13.74
41.03 33.98 28.67
1.90 8.79* 14.93*
*P , 0.05.
e452
| www.jorthotrauma.com
DISCUSSION Although vitamin D therapy improved the majority of the patients’ serum 25-OH vitamin D with initial insufficiency or deficiency, it was not as successful as we hoped. Patients with initial deficiency and insufficiency had the largest improvements but neither normalized. However, there were significant changes in the levels for those with the lowest levels of 25-OH vitamin D. Vitamin D deficiency is estimated to affect about 1 billion people worldwide and is linked to multiple medical maladies including cancer, diabetes, cardiovascular disease, and musculoskeletal health.11 Vitamin D deficiency has been associated with fragility fractures3 and tibial nonunions.4 Approximately 40% of elective sports-related orthopaedic surgery patients have low vitamin D levels.12 However, the direct consequence of having a low serum 25-OH vitamin D level and an orthopaedic injury—such as fracture nonunion or infection—is unknown. The limitations of this study go beyond its retrospective nature. Medication adherence, even with a prescription from a physician, ranges from 19% to 100%.13 Patients with low serum 25-OH vitamin D were given a prescription for weekly ergocalciferol, and all patients were given the recommendation for over-the-counter daily supplementation of calcium and vitamin D. Patients were asked at each clinic visit if they were taking the medications as recommended and were entered in their medical record. However, even in the best of circumstances, adherence to treatment was not validated with pill counts. Therefore, the efficacy of the treatment regimen would have been more accurate with more strict protocols. Furthermore, there is the natural fluctuation in vitamin D levels in normal healthy adults. Melin et al14 monitored vitamin D levels and the bone mineral density (BMD) of patient’s femoral necks over a 12-month period. There was a regular fluctuation of vitamin D levels with higher levels in the months after summer and lower levels in months after winter. There was a statistically significant positive correlation of vitamin D levels and femoral neck BMD across the study group, but there was no significant change in BMD with change in vitamin D levels. What can be acknowledged from this and other articles is that low vitamin D levels are common among many different patients and that these levels are not static. Establishing the best way to restore normal levels quickly and safely may be an adjunct to our orthopaedic care —not only in trauma patients but also in patients who require bone growth (eg, bone tendon bone allograft healing or bony ongrowth for arthroplasty). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
J Orthop Trauma Volume 29, Number 11, November 2015
Effectiveness of Vitamin D in Orthopaedic Trauma
Our study indicates that continued vigilance is required to adequately treat a low serum 25-OH vitamin D level. Treating vitamin D insufficiency or deficiency with a standard regimen does raise serum levels, but more effective regimens and closer monitoring is required. Understanding the actual complications associated with low vitamin D in fracture patients is also important because most fractures do heal despite a significant number of patients with low serum 25-OH vitamin D. Future studies will prospectively evaluate treatment regimens and the effect of low vitamin D on complications of orthopaedic trauma. We will also study ways on why these patients’ fracture healing patterns did or did not respond to regimental vitamin D treatments.
5. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135:317–322. 6. Crist BD, Hood M, Della Rocca GJ, et al. Prevalence of Vitamin D Insufficiency in Orthopaedic Trauma Patients. Minneapolis, MN: OTA Annual Meeting; 2012. 7. Dietary Reference Intakes: A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients. Washington, DC: The National Academies Press; 1998. 8. Hollis BW, Wagner CL. Normal serum vitamin D levels. N Engl J Med. 2005;352:515–516; author reply 515–516. 9. Hathcock JN, Shao A, Vieth R, et al. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85:6–18. 10. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911–1930. 11. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777–783. 12. Bogunovic L, Kim AD, Beamer BS, et al. Hypovitaminosis D in patients scheduled to undergo orthopaedic surgery: a single-center analysis. J Bone Joint Surg Am. 2010;92:2300–2304. 13. Farmer KC. Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin Ther. 1999;21: 1074–1090; discussion 1073. 14. Melin A, Wilske J, Ringertz H, et al. Seasonal variations in serum levels of 25-hydroxyvitamin D and parathyroid hormone but no detectable change in femoral neck bone density in an older population with regular outdoor exposure. J Am Geriatr Soc. 2001;49:1190–1196.
REFERENCES 1. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80:1689S–1696S. 2. Hsu JJ, Tintut Y, Demer LL. Vitamin D and osteogenic differentiation in the artery wall. Clin J Am Soc Nephrol. 2008;3:1542–1547. 3. Bischoff-Ferrari HA, Can U, Staehelin HB, et al. Severe vitamin D deficiency in Swiss hip fracture patients. Bone. 2008;42:597–602. 4. Brinker MR, OConnor DP. Outcomes of tibial nonunion in older adults following treatment using the Ilizarov method. J Orthop Trauma. 2007; 21:634–642.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jorthotrauma.com |
e453
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Effectiveness of Vitamin D Therapy in Orthopaedic Trauma Patients Daniel S. Robertson, MD,* Tyler Jenkins, MD,† Yvonne M. Murtha, MD,‡ Gregory J. Della Rocca, MD, PhD,‡ David A. Volgas, MD,‡ James P. Stannard, MD,‡ and Brett D. Crist, MD‡
Objective: The purpose of this study was to determine the
Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
effectiveness of our vitamin D treatment protocol in managing low serum vitamin D levels in orthopaedic trauma patients.
(J Orthop Trauma 2015;29:e451–e453)
Methods: A retrospective review was conducted of all orthopaedic trauma patients at a university level I trauma center over 20 months. Patients were included if they had an initial and repeat 25-hydroxy (OH) vitamin D serum level available. Vitamin D deficiency was defined as serum 25-hydroxy vitamin D level with less than 20 ng/mL. Vitamin D insufficiency was defined as serum 25-hydroxy vitamin D level between 20 and 32 ng/mL. The standard regimen for all patients was over-the-counter vitamin D3 1000 IU and 1500 mg of calcium daily. Patients with vitamin D deficiency or insufficiency also received 50,000 IU of ergocalciferol (D2) weekly until their 25-hydroxyvitamin D level normalized or their fracture healed. No compliance monitoring was performed except for questioning at each clinic visit.
Results: A total of 201 patients met the inclusion criteria. Thirtytwo patients had a normal initial 25-hydroxyvitamin D level, and 84% maintained their normal level, whereas 16% became insufficient or deficient. There were 88 patients insufficient initially and 54.5% improved to normal and 8% became deficient. In the vitamin D deficiency group (81), 26% remained deficient and 74% improved to insufficient. The average increase in serum 25-OH vitamin D with treatment (in nanograms per milliliter) was statistically significant for both the insufficient and deficient groups.
Conclusions: Vitamin D therapy improved the majority of the patients’ vitamin D-25-OH level but did not normalize most. Patients with initial deficiency had the largest improvement. This study indicates that vigilance is required to adequately treat a low serum vitamin D-25-OH level. Key Words: vitamin D deficiency, musculoskeletal trauma, fracture healing Accepted for publication June 1, 2015. From the *Department of Orthopaedics, University of Texas Health Science Center at San Antonio, San Antonio, TX; †Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL; and ‡Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, MO. Presented at the Orthopaedic Trauma Association, Annual Meeting, October 12, 2013, Phoenix, AZ. The authors report no conflict of interest. Reprints: Brett D. Crist, MD, Department of Orthopaedic Surgery, University of Missouri, One Hospital Drive, N119, Columbia, MO 65212 (e-mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Orthop Trauma Volume 29, Number 11, November 2015
INTRODUCTION Vitamin D is an important prohormone in the regulation and maintenance of numerous physiologic systems in the human. It plays a role in cardiac, immune, digestive systems, and the musculoskeletal system.1,2 Low vitamin D levels are associated with a higher incidence of fracture in the elderly3 and recalcitrant tibial nonunions.4 At our institution, we reviewed our orthopaedic trauma patients with fractures who had serum 25-hydroxy (25-OH) vitamin levels available over a 20-month period. Records for 889 patients were reviewed, and 77% of them had either 25OH vitamin D deficiency or insufficiency, as defined by Hollis.5,6 During this review period, it was noted that a significant number of patients had a low serum 25-OH vitamin D level. Based on these findings and its potential implications in patient outcomes, our center implemented a protocol-driven effort to supplement patients during the fracture healing period. The purpose of this study was to evaluate the effectiveness of our vitamin D treatment protocol in orthopaedic trauma patients. Our hypothesis was that vitamin D therapy normalized serum 25-OH vitamin D levels.
PATIENTS AND METHODS After institutional review board approval, a retrospective review was performed for all orthopaedic trauma patients with a fracture at our American College of Surgeons verified level I university trauma center from January 1, 2009 to September 30, 2010. Patient inclusion criteria were they had to be at least 18 years old, they had a fracture managed by one of 4 attending orthopaedic trauma surgeons, and they had an available serum 25-OH vitamin D level available within 2 weeks from their injury and a repeat 25-OH vitamin D level available. The 25-OH form of vitamin D is the inactive serum form but is found to be the most accurate measure of systemic vitamin D levels.7 During the review period when serum vitamin D levels were obtained, the standard regimen for all patients was over-the-counter vitamin D3 1000 IU and 1500 mg of calcium daily. Patients with serum 25-OH vitamin D deficiency or insufficiency8 also received an 8-week prescription www.jorthotrauma.com |
e451
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Robertson et al
J Orthop Trauma Volume 29, Number 11, November 2015
for weekly 50,000 IU ergocalciferol (D2) until their 25-OH vitamin D level normalized or their fracture healed, which correlated with the risk assessment performed by Hathcock et al.9 No complications were noted. Patients with either a history of hypercalcemia or at risk for hypercalcemia—noted as calcium levels higher than 10.5 mg/dL—were excluded from this regimen. Standard clinic follow-up was performed at 2-, 6-, and 12-week visits and then every 2–3 months until fracture healing occurred. Follow-up serum 25-OH vitamin D levels were encouraged after the 8-week course of ergocalciferol, per our protocol. No compliance monitoring was performed except for questioning at each clinic visit. We gave calcium and vitamin D supplementation prescriptions when patients left the hospital and on follow-up verified that these were on their medication lists. We then provided patients information on over-the-counter calcium and vitamin D supplements and the required amounts they needed to take.
the insufficient group improved to normal, and 7 patients (8%) became deficient. The remaining 33 patients (37.5%) remained insufficient. The average change for the insufficient group was an increase of 8.79 ng/mL with treatment and was statistically significant (P , 0.05). Of the 81 patients with 25OH vitamin D deficiency, 26% (21) remained deficient and 74% (60) improved to the insufficient level. The deficient group had the largest average increase of 14.93 ng/mL and was also statistically significant (P , 0.05). Follow-up values were determined after 8 weeks of therapy.
Statistical Methods Descriptive statistics including the mean, median, and mode were calculated. A x2 test was performed if all cell frequencies were greater than 5. The Fisher exact probability test was used if any of the cell frequencies were 5 or less. We performed 1-sample T tests to calculate significant change in values. P values ,0.05 were considered statistically significant.
Definitions Vitamin D deficiency was defined as serum 25-hydroxy vitamin D level with less than 20 ng/mL. Vitamin D insufficiency was defined as serum 25-hydroxy vitamin D level between 20 and 32 ng/mL.8 By comparison, the Institute of Medicine and the Endocrine Society define deficiency as less than 20 ng/mL and between 21–29 ng/mL, respectively.10
RESULTS Two hundred one patients had initial and repeat serum 25-OH vitamin D levels. Of the 32 patients with a normal initial 25-OH vitamin D level, 84% (27) remained normal and 16% (5) became insufficient or deficient during clinical follow-up (Table 1). The average change in 25-OH vitamin D levels for this subgroup was an increase of 1.9 ng/mL and was not statistically significant (P = 0.17). The insufficient group consisted of 88 patients. Forty-eight patients (54.5%) in
TABLE 1. Initial Serum 25-OH Vitamin D Levels for Each Patient Group, Follow-up Vitamin D Levels, and Average Change
Vitamin D-25-OH Level Normal ($32 ng/mL) Insufficiency (,32 ng/mL) Deficiency (,20 ng/mL)
Average Initial Vitamin D-25 Level, ng/mL
Average Repeat Vitamin D-25 Level, ng/mL
Average Increase in Vitamin D-25 Level, ng/mL
39.13 25.19 13.74
41.03 33.98 28.67
1.90 8.79* 14.93*
*P , 0.05.
e452
| www.jorthotrauma.com
DISCUSSION Although vitamin D therapy improved the majority of the patients’ serum 25-OH vitamin D with initial insufficiency or deficiency, it was not as successful as we hoped. Patients with initial deficiency and insufficiency had the largest improvements but neither normalized. However, there were significant changes in the levels for those with the lowest levels of 25-OH vitamin D. Vitamin D deficiency is estimated to affect about 1 billion people worldwide and is linked to multiple medical maladies including cancer, diabetes, cardiovascular disease, and musculoskeletal health.11 Vitamin D deficiency has been associated with fragility fractures3 and tibial nonunions.4 Approximately 40% of elective sports-related orthopaedic surgery patients have low vitamin D levels.12 However, the direct consequence of having a low serum 25-OH vitamin D level and an orthopaedic injury—such as fracture nonunion or infection—is unknown. The limitations of this study go beyond its retrospective nature. Medication adherence, even with a prescription from a physician, ranges from 19% to 100%.13 Patients with low serum 25-OH vitamin D were given a prescription for weekly ergocalciferol, and all patients were given the recommendation for over-the-counter daily supplementation of calcium and vitamin D. Patients were asked at each clinic visit if they were taking the medications as recommended and were entered in their medical record. However, even in the best of circumstances, adherence to treatment was not validated with pill counts. Therefore, the efficacy of the treatment regimen would have been more accurate with more strict protocols. Furthermore, there is the natural fluctuation in vitamin D levels in normal healthy adults. Melin et al14 monitored vitamin D levels and the bone mineral density (BMD) of patient’s femoral necks over a 12-month period. There was a regular fluctuation of vitamin D levels with higher levels in the months after summer and lower levels in months after winter. There was a statistically significant positive correlation of vitamin D levels and femoral neck BMD across the study group, but there was no significant change in BMD with change in vitamin D levels. What can be acknowledged from this and other articles is that low vitamin D levels are common among many different patients and that these levels are not static. Establishing the best way to restore normal levels quickly and safely may be an adjunct to our orthopaedic care —not only in trauma patients but also in patients who require bone growth (eg, bone tendon bone allograft healing or bony ongrowth for arthroplasty). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
J Orthop Trauma Volume 29, Number 11, November 2015
Effectiveness of Vitamin D in Orthopaedic Trauma
Our study indicates that continued vigilance is required to adequately treat a low serum 25-OH vitamin D level. Treating vitamin D insufficiency or deficiency with a standard regimen does raise serum levels, but more effective regimens and closer monitoring is required. Understanding the actual complications associated with low vitamin D in fracture patients is also important because most fractures do heal despite a significant number of patients with low serum 25-OH vitamin D. Future studies will prospectively evaluate treatment regimens and the effect of low vitamin D on complications of orthopaedic trauma. We will also study ways on why these patients’ fracture healing patterns did or did not respond to regimental vitamin D treatments.
5. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135:317–322. 6. Crist BD, Hood M, Della Rocca GJ, et al. Prevalence of Vitamin D Insufficiency in Orthopaedic Trauma Patients. Minneapolis, MN: OTA Annual Meeting; 2012. 7. Dietary Reference Intakes: A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients. Washington, DC: The National Academies Press; 1998. 8. Hollis BW, Wagner CL. Normal serum vitamin D levels. N Engl J Med. 2005;352:515–516; author reply 515–516. 9. Hathcock JN, Shao A, Vieth R, et al. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85:6–18. 10. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911–1930. 11. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777–783. 12. Bogunovic L, Kim AD, Beamer BS, et al. Hypovitaminosis D in patients scheduled to undergo orthopaedic surgery: a single-center analysis. J Bone Joint Surg Am. 2010;92:2300–2304. 13. Farmer KC. Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin Ther. 1999;21: 1074–1090; discussion 1073. 14. Melin A, Wilske J, Ringertz H, et al. Seasonal variations in serum levels of 25-hydroxyvitamin D and parathyroid hormone but no detectable change in femoral neck bone density in an older population with regular outdoor exposure. J Am Geriatr Soc. 2001;49:1190–1196.
REFERENCES 1. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80:1689S–1696S. 2. Hsu JJ, Tintut Y, Demer LL. Vitamin D and osteogenic differentiation in the artery wall. Clin J Am Soc Nephrol. 2008;3:1542–1547. 3. Bischoff-Ferrari HA, Can U, Staehelin HB, et al. Severe vitamin D deficiency in Swiss hip fracture patients. Bone. 2008;42:597–602. 4. Brinker MR, OConnor DP. Outcomes of tibial nonunion in older adults following treatment using the Ilizarov method. J Orthop Trauma. 2007; 21:634–642.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jorthotrauma.com |
e453
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
