- Email: [email protected]
Vitamin D Deficiency and Chronic Pain Cause and Effect or Epiphenomenon?: In Response
Mayo Clin Proc, May 2004, Vol 79
The draconian message that people should never be exposed to sunlight without sun protection is totally unwarranted and should be replaced with the message that sensible sun exposure is good for overall health and well-being. Hypovitaminosis D has been linked not only to increased risk of tuberculosis, as noted by Dr Padda, but also to increased risk of type 1 diabetes, hypertension, congestive heart failure, and cancers of the colon, breast, prostate, ovaries, and other organs.1,8 Thus, I hope that the study reported by Plotnikoff and Quigley9 has enlightened physicians about how common and underdiagnosed hypovitaminosis D is and about its consequences on bone and muscle health. Michael F. Holick, PhD, MD Boston University School of Medicine Boston, Mass 1. 2. 3.
4. 5. 6. 7. 8. 9.
Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes. 2002;9:87-98. Veierød MB, Weiderpass E, Thörn M, et al. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst. 2003;95:1530-1538. Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Am J Clin Nutr. 2003;77: 1478-1483. Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int. 1998;8:222-230. Reid IR, Gallagher DJ, Bosworth J. Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure. Age Ageing. 1986;15:35-40. Chel VG, Ooms ME, Popp-Snijders C, et al. Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly. J Bone Miner Res. 1998;13:1238-1242. Chuck A, Todd J, Diffey B. Subliminal ultraviolet-B irradiation for the prevention of vitamin D deficiency in the elderly: a feasibility study. Photodermatol Photoimmunol Photomed. 2001;17:168-171. Grant WB. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002;94: 1867-1875. Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc. 2003;78:1463-1470.
Vitamin D Deficiency and Chronic Pain: Cause and Effect or Epiphenomenon? To the Editor: Because of the article on hypovitaminosis D in the December 2003 issue of Mayo Clinic Proceedings, I now have patients with chronic pain requesting measurement of their vitamin D levels in addition to the usual list of unjustified tests. Plotnikoff and Quigley1 propose that the management of an exceedingly common condition—musculoskeletal pain of indeterminate origin—should include a routine assessment of vitamin D status. This conclusion is not supported by any data presented in the article, and the accompanying editorial by Holick2 challenges none of the authors’ hypotheses. The patient group analyzed in the study—patients with “persistent, nonspecific musculoskeletal pain”—is by definition an amalgam of disparate physical and emotional problems. The presence of biochemical vitamin D deficiency in this group indi-
Letters to the Editor
695
cates only that such a deficiency can be recognized commonly in Minnesota. In the absence of a concurrent comparison group, the study says nothing about whether vitamin D deficiency is more common in such patients than in the population at large or whether it has any role in causation. The comparison groups provided from historical controls are predominantly white, and it is not surprising that their 25-hydroxyvitamin D levels are higher than those of the selected ethnic groups in this study. Furthermore, this hypothesis immediately leads to several conclusions that are inconsistent with observed patterns of illness. If vitamin D deficiency is an important contributor to chronic musculoskeletal pain, why is the incidence of the disorder not profoundly different in different races once socioeconomic status is accounted for? Similarly, why is there no dramatic decrease in the incidence of chronic musculoskeletal pain on moving from northern to southern latitudes? Working as a rheumatologist in Tennessee, I am unfortunately certain that this entity is not a rare diagnosis in the South. Before proposing a new clinical care standard for a common health problem, a confirmatory case-control study followed by an evaluation of the effects of vitamin D repletion would be advisable. To quote the authors, “The findings may simply reflect the background prevalence of hypovitaminosis D.” Kevin J. Myers, MD Arthritis Specialists of Nashville, Inc Nashville, Tenn 1. 2.
Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc. 2003;78:1463-1470. Holick MF. Vitamin D deficiency: what a pain it is [editorial]. Mayo Clin Proc. 2003;78:1457-1459.
In reply: Dr Myers’ letter questions the value of quantified serum vitamin D levels in patients with musculoskeletal pain of indeterminate origin. He asserts that such pain is, by definition, an amalgam of disparate physical and emotional problems. This is unfortunate. By definition, physical problems are determinable and “emotional problems” are diagnoses of exclusion. In Table 2 in our article, we summarized findings in 5 of our patients with pain of indeterminate origin. Although these patients had consumed considerable health care resources with minimal benefit, no one had considered and ruled out a known cause of their musculoskeletal pain symptoms, osteomalacia. At best, these 5 patients had vitamin D levels of only 2 ng/mL (the lowest level of detection is 3 ng/mL). Surprisingly, 3 were women of childbearing age. Dr Myers assumes that residents of Nashville, Tenn (36° north), are not at risk of vitamin D deficiency. However, significant deficiency in young people has been documented at similar latitudes in both the boreal hemisphere (including Beirut, Lebanon [34° north],1 and Niigata, Japan [38° north]2) and the austral hemisphere (including Melbourne [37° south] and Sydney [34° south], Australia,3,4 and Buenos Aires, Argentina [34° south]5). This is true despite the austral hemisphere’s approximately 2° difference in effective latitude (W. B. Grant, PhD, personal communication, February 2004). Even at 33° south (Cape
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
696
Letters to the Editor
Mayo Clin Proc, May 2004, Vol 79
Town, South Africa), winter sun has comparatively less than one third the capacity of summer sunlight to promote production of vitamin D.6 Furthermore, this limited capacity is restricted to precisely the hours that people are urged to avoid the sun. Although vitamin D deficiency in young people across the United States is significant,7 we cannot afford to screen everyone. However, can we afford $10 to $15 billion each year in direct costs for treatment of osteoporosis and its complications?8 Our study justifies screening patients with persistent, nonspecific musculoskeletal pain because it documented that many patients considered at low risk for vitamin D deficiency were, in fact, severely or even profoundly deficient. Testing does not place the patient at risk—failure to diagnose deficiency may. Gregory A. Plotnikoff, MD, MTS Keio University Medical School Tokyo, Japan 1. 2. 3. 4. 5.
6. 7.
8.
Gannage-Yared MH, Chemali R, Yaacoub N, Halaby G. Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res. 2000;15:1856-1862. Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-hydroxyvitamin D in young adult Japanese women: a cross sectional study. Nutrition. 2001;17:921-925. Nozza JM, Rodda CP. Vitamin D deficiency in mothers of infants with rickets. Med J Aust. 2001;175:253-255. Lipson T. Epidemic rickets in migrant families in Melbourne and Sydney. J Paediatr Child Health. 1995;31:483-484. Fassi J, Russo Picasso MF, Furci A, Sorroche P, Jauregui R, Plantalech L. Seasonal variations in 25-hydroxyvitamin D in young and elderly and populations in Buenos Aires City [in Spanish]. Medicina (B Aires). 2003;63:215-220. Pettifor JM, Moodley GP, Hough FS, et al. The effect of season and latitude on in vitro vitamin D formation by sunlight in South Africa. S Afr Med J. 1996;86:1270-1272. Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002;76:187-192. National Institutes of Health Consensus Development Panel. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement. 2000;17(1):7.
In reply: Dr Myers makes several good points about the incidence of nonspecific musculoskeletal pain as it relates to race, socioeconomic class, and latitude. Unfortunately, what he does not take into account is that vitamin D deficiency is common and widespread in both children and adults of all races throughout the United States.1,2 In many patients (especially those with lower socioeconomic status) who complain of muscle aches and bone pain, these symptoms are simply dismissed by their doctors, or more urgent concomitant medical problems overshadow these nonspecific complaints, which are discounted or considered associated with the patient’s poor health. Malabanan et al3 reported that an African American woman with excruciating bone pain and muscle aches responded dramatically to vitamin D therapy; the bone pain and muscle discomfort resolved completely, and she had a 25% increase in bone density in just 2 years. Gloth et al4 and Glerup et al5 reported that bone pain and myopathy are common features of vitamin D deficiency, and Bischoff et al6 reported that muscle weakness is commonly associated with vitamin D deficiency. Thus, substantial data in
the literature support the role of vitamin D deficiency in the nonspecific musculoskeletal pain syndrome. Myers may be unaware that the lower limit of the 25-hydroxyvitamin D assay that is used to determine vitamin D status is inadequate. A 25hydroxyvitamin D level of less than 20 ng/mL should be considered as vitamin D deficiency, not the less than 10 ng/mL level that most commercial laboratories report.7-9 Furthermore, a 25-hydroxyvitamin D level of between 30 and 50 ng/mL is preferred.10 I suspect that most of Myers’ patients are vitamin D deficient, which is why he has not appreciated the relationship between vitamin D deficiency and the nonspecific musculoskeletal pain syndrome. I agree that a controlled trial should be conducted to define the role of vitamin D deficiency in nonspecific musculoskeletal pain that is not associated with a rheumatologic disorder. Finally, in my experience, patients who receive 50,000 IU of vitamin D once or twice a month feel better, and when they stop the medication, they often develop muscle weakness and nonspecific aches and discomfort. I encourage Dr Myers to prescribe this regimen for his patients. Michael F. Holick, PhD, MD Boston University School of Medicine Boston, Mass 1.
2. 3. 4. 5. 6. 7. 8.
9. 10.
Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002;76: 187-192. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362-371. Malabanan AO, Turner AK, Holick MF. Severe generalized bone pain and osteoporosis in a premenopausal black female: effect of vitamin D replacement. J Clin Densitom. 1998;1:201-204. Gloth FM III, Lindsay JM, Zelesnick LB, Greenough WB III. Can vitamin D deficiency produce an unusual pain syndrome? Arch Intern Med. 1991;151:1662-1664. Glerup H, Mikkelsen K, Poulsen L, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med. 2000;247:260-268. Bischoff HA, Stahelin HB, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18:343-351. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency [letter]. Lancet. 1998;351:805-806. Souberbielle JC, Lawson-Body E, Hammadi B, Sarfati E, Kahan A, Cormier C. The use in clinical practice of parathyroid hormone normative values established in vitamin D-sufficient subjects. J Clin Endocrinol Metab. 2003;88:3501-3504. Holick MF. The parathyroid hormone D-lema [editorial]. J Clin Endocrinol Metab. 2003;88:3499-3500. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003;22:142-146.
Vitamin D Deficiency as a Contributor to Multiple Forms of Chronic Pain To the Editor: It was a delight to see another description of the association between vitamin D deficiency and pain in the medical literature. My colleagues and I published an early, if not the first, description of non–osteomalacia-related pain in the Archives of Internal Medicine in 19911 and recently reviewed this
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
The draconian message that people should never be exposed to sunlight without sun protection is totally unwarranted and should be replaced with the message that sensible sun exposure is good for overall health and well-being. Hypovitaminosis D has been linked not only to increased risk of tuberculosis, as noted by Dr Padda, but also to increased risk of type 1 diabetes, hypertension, congestive heart failure, and cancers of the colon, breast, prostate, ovaries, and other organs.1,8 Thus, I hope that the study reported by Plotnikoff and Quigley9 has enlightened physicians about how common and underdiagnosed hypovitaminosis D is and about its consequences on bone and muscle health. Michael F. Holick, PhD, MD Boston University School of Medicine Boston, Mass 1. 2. 3.
4. 5. 6. 7. 8. 9.
Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes. 2002;9:87-98. Veierød MB, Weiderpass E, Thörn M, et al. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst. 2003;95:1530-1538. Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Am J Clin Nutr. 2003;77: 1478-1483. Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int. 1998;8:222-230. Reid IR, Gallagher DJ, Bosworth J. Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure. Age Ageing. 1986;15:35-40. Chel VG, Ooms ME, Popp-Snijders C, et al. Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly. J Bone Miner Res. 1998;13:1238-1242. Chuck A, Todd J, Diffey B. Subliminal ultraviolet-B irradiation for the prevention of vitamin D deficiency in the elderly: a feasibility study. Photodermatol Photoimmunol Photomed. 2001;17:168-171. Grant WB. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002;94: 1867-1875. Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc. 2003;78:1463-1470.
Vitamin D Deficiency and Chronic Pain: Cause and Effect or Epiphenomenon? To the Editor: Because of the article on hypovitaminosis D in the December 2003 issue of Mayo Clinic Proceedings, I now have patients with chronic pain requesting measurement of their vitamin D levels in addition to the usual list of unjustified tests. Plotnikoff and Quigley1 propose that the management of an exceedingly common condition—musculoskeletal pain of indeterminate origin—should include a routine assessment of vitamin D status. This conclusion is not supported by any data presented in the article, and the accompanying editorial by Holick2 challenges none of the authors’ hypotheses. The patient group analyzed in the study—patients with “persistent, nonspecific musculoskeletal pain”—is by definition an amalgam of disparate physical and emotional problems. The presence of biochemical vitamin D deficiency in this group indi-
Letters to the Editor
695
cates only that such a deficiency can be recognized commonly in Minnesota. In the absence of a concurrent comparison group, the study says nothing about whether vitamin D deficiency is more common in such patients than in the population at large or whether it has any role in causation. The comparison groups provided from historical controls are predominantly white, and it is not surprising that their 25-hydroxyvitamin D levels are higher than those of the selected ethnic groups in this study. Furthermore, this hypothesis immediately leads to several conclusions that are inconsistent with observed patterns of illness. If vitamin D deficiency is an important contributor to chronic musculoskeletal pain, why is the incidence of the disorder not profoundly different in different races once socioeconomic status is accounted for? Similarly, why is there no dramatic decrease in the incidence of chronic musculoskeletal pain on moving from northern to southern latitudes? Working as a rheumatologist in Tennessee, I am unfortunately certain that this entity is not a rare diagnosis in the South. Before proposing a new clinical care standard for a common health problem, a confirmatory case-control study followed by an evaluation of the effects of vitamin D repletion would be advisable. To quote the authors, “The findings may simply reflect the background prevalence of hypovitaminosis D.” Kevin J. Myers, MD Arthritis Specialists of Nashville, Inc Nashville, Tenn 1. 2.
Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc. 2003;78:1463-1470. Holick MF. Vitamin D deficiency: what a pain it is [editorial]. Mayo Clin Proc. 2003;78:1457-1459.
In reply: Dr Myers’ letter questions the value of quantified serum vitamin D levels in patients with musculoskeletal pain of indeterminate origin. He asserts that such pain is, by definition, an amalgam of disparate physical and emotional problems. This is unfortunate. By definition, physical problems are determinable and “emotional problems” are diagnoses of exclusion. In Table 2 in our article, we summarized findings in 5 of our patients with pain of indeterminate origin. Although these patients had consumed considerable health care resources with minimal benefit, no one had considered and ruled out a known cause of their musculoskeletal pain symptoms, osteomalacia. At best, these 5 patients had vitamin D levels of only 2 ng/mL (the lowest level of detection is 3 ng/mL). Surprisingly, 3 were women of childbearing age. Dr Myers assumes that residents of Nashville, Tenn (36° north), are not at risk of vitamin D deficiency. However, significant deficiency in young people has been documented at similar latitudes in both the boreal hemisphere (including Beirut, Lebanon [34° north],1 and Niigata, Japan [38° north]2) and the austral hemisphere (including Melbourne [37° south] and Sydney [34° south], Australia,3,4 and Buenos Aires, Argentina [34° south]5). This is true despite the austral hemisphere’s approximately 2° difference in effective latitude (W. B. Grant, PhD, personal communication, February 2004). Even at 33° south (Cape
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
696
Letters to the Editor
Mayo Clin Proc, May 2004, Vol 79
Town, South Africa), winter sun has comparatively less than one third the capacity of summer sunlight to promote production of vitamin D.6 Furthermore, this limited capacity is restricted to precisely the hours that people are urged to avoid the sun. Although vitamin D deficiency in young people across the United States is significant,7 we cannot afford to screen everyone. However, can we afford $10 to $15 billion each year in direct costs for treatment of osteoporosis and its complications?8 Our study justifies screening patients with persistent, nonspecific musculoskeletal pain because it documented that many patients considered at low risk for vitamin D deficiency were, in fact, severely or even profoundly deficient. Testing does not place the patient at risk—failure to diagnose deficiency may. Gregory A. Plotnikoff, MD, MTS Keio University Medical School Tokyo, Japan 1. 2. 3. 4. 5.
6. 7.
8.
Gannage-Yared MH, Chemali R, Yaacoub N, Halaby G. Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res. 2000;15:1856-1862. Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-hydroxyvitamin D in young adult Japanese women: a cross sectional study. Nutrition. 2001;17:921-925. Nozza JM, Rodda CP. Vitamin D deficiency in mothers of infants with rickets. Med J Aust. 2001;175:253-255. Lipson T. Epidemic rickets in migrant families in Melbourne and Sydney. J Paediatr Child Health. 1995;31:483-484. Fassi J, Russo Picasso MF, Furci A, Sorroche P, Jauregui R, Plantalech L. Seasonal variations in 25-hydroxyvitamin D in young and elderly and populations in Buenos Aires City [in Spanish]. Medicina (B Aires). 2003;63:215-220. Pettifor JM, Moodley GP, Hough FS, et al. The effect of season and latitude on in vitro vitamin D formation by sunlight in South Africa. S Afr Med J. 1996;86:1270-1272. Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002;76:187-192. National Institutes of Health Consensus Development Panel. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement. 2000;17(1):7.
In reply: Dr Myers makes several good points about the incidence of nonspecific musculoskeletal pain as it relates to race, socioeconomic class, and latitude. Unfortunately, what he does not take into account is that vitamin D deficiency is common and widespread in both children and adults of all races throughout the United States.1,2 In many patients (especially those with lower socioeconomic status) who complain of muscle aches and bone pain, these symptoms are simply dismissed by their doctors, or more urgent concomitant medical problems overshadow these nonspecific complaints, which are discounted or considered associated with the patient’s poor health. Malabanan et al3 reported that an African American woman with excruciating bone pain and muscle aches responded dramatically to vitamin D therapy; the bone pain and muscle discomfort resolved completely, and she had a 25% increase in bone density in just 2 years. Gloth et al4 and Glerup et al5 reported that bone pain and myopathy are common features of vitamin D deficiency, and Bischoff et al6 reported that muscle weakness is commonly associated with vitamin D deficiency. Thus, substantial data in
the literature support the role of vitamin D deficiency in the nonspecific musculoskeletal pain syndrome. Myers may be unaware that the lower limit of the 25-hydroxyvitamin D assay that is used to determine vitamin D status is inadequate. A 25hydroxyvitamin D level of less than 20 ng/mL should be considered as vitamin D deficiency, not the less than 10 ng/mL level that most commercial laboratories report.7-9 Furthermore, a 25-hydroxyvitamin D level of between 30 and 50 ng/mL is preferred.10 I suspect that most of Myers’ patients are vitamin D deficient, which is why he has not appreciated the relationship between vitamin D deficiency and the nonspecific musculoskeletal pain syndrome. I agree that a controlled trial should be conducted to define the role of vitamin D deficiency in nonspecific musculoskeletal pain that is not associated with a rheumatologic disorder. Finally, in my experience, patients who receive 50,000 IU of vitamin D once or twice a month feel better, and when they stop the medication, they often develop muscle weakness and nonspecific aches and discomfort. I encourage Dr Myers to prescribe this regimen for his patients. Michael F. Holick, PhD, MD Boston University School of Medicine Boston, Mass 1.
2. 3. 4. 5. 6. 7. 8.
9. 10.
Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002;76: 187-192. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362-371. Malabanan AO, Turner AK, Holick MF. Severe generalized bone pain and osteoporosis in a premenopausal black female: effect of vitamin D replacement. J Clin Densitom. 1998;1:201-204. Gloth FM III, Lindsay JM, Zelesnick LB, Greenough WB III. Can vitamin D deficiency produce an unusual pain syndrome? Arch Intern Med. 1991;151:1662-1664. Glerup H, Mikkelsen K, Poulsen L, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med. 2000;247:260-268. Bischoff HA, Stahelin HB, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18:343-351. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency [letter]. Lancet. 1998;351:805-806. Souberbielle JC, Lawson-Body E, Hammadi B, Sarfati E, Kahan A, Cormier C. The use in clinical practice of parathyroid hormone normative values established in vitamin D-sufficient subjects. J Clin Endocrinol Metab. 2003;88:3501-3504. Holick MF. The parathyroid hormone D-lema [editorial]. J Clin Endocrinol Metab. 2003;88:3499-3500. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003;22:142-146.
Vitamin D Deficiency as a Contributor to Multiple Forms of Chronic Pain To the Editor: It was a delight to see another description of the association between vitamin D deficiency and pain in the medical literature. My colleagues and I published an early, if not the first, description of non–osteomalacia-related pain in the Archives of Internal Medicine in 19911 and recently reviewed this
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.