DNC NEWS: Strokes, bone loss and vitamin D
There is a relationship between strokes, bone loss and vitamin D that is proving more complex than originally thought and which is just now starting to be explained.
Elderly people who have strokes are 2-4 times more likely to break a hip after the stroke. [i] The first assumption was that after a stroke people were less stable on their feet, more likely to totter, fall and break something. The second assumption was that after a stroke people are often confined to beds for extended periods, a known cause of bone density loss. Good guesses but wrong.
As good as these explanations sound, the real answer is proving to be more complex. I wrote last year about the relationship between vitamin D levels and hip fractures. At the time new data was suggesting that it wasn't the variation in bone mineral density produced by vitamin D that was of benefit in preventing fractures, but over the short term it was the increase in leg muscle strength that protected the elderly from falling and breaking bones.
Research now shows that people recovering from strokes have less vitamin D in their bodies than do healthy people their ages. The low vitamin D level could explain why stroke patients lose bone density so fast after a stroke.
Warburton and her colleagues working in Cambridge , England looked at 34 stroke patients, average age 72 and 96 healthy people matched in age, gender, and other characteristics. Blood samples showed that the stroke patients had one third less vitamin D in their blood than non stroke patients. In the first months after the stroke, vitamin D concentrations were so low as to be “off the scale.” [ii]
“Off the scale” sounds rather extreme. Yet it may be so. Following a stroke a patient is typically immobilized in a hospital bed. While in bed the skeletal bones lose calcium quickly. This increases blood levels of calcium. In response to this surge of calcium, the body responds by decreasing vitamin D production. If one started out with low vitamin D, this induced drop may be enough to push one off the scale. [iii]
Are low vitamin D levels a result of the stroke or a cause of the stroke in the first place? Low vitamin D levels have been theorized as contributing to strokes by increasing parathyroid hormone levels. The level of Vitamin D in the blood seesaws with parathyroid hormone. If vitamin D levels are low, parathyroid levels increase. Elevated parathyroid hormone often causes an increase in blood pressure [iv] and thus theoretically stroke. It may be that low vitamin D actually may be a contributing factor in strokes. [v]
It looks like vitamin D deficiency is a far bigger problem than we thought especially in older populations. Estimates have ranged as high as 60% of hospitalized patients are Vitamin D deficient. A study done in Israel suggests that even in a sunny climate almost a quarter of hospitalized patients are vitamin D deficient. [vi] Yet as high as this sounds, these may be seriously underestimating the problem. For example in the Israeli study, low vitamin D was defined as serum 25(OH) vitamin D of less than 15 ng/ml or 37.5 nmol/L. Yet Last year, in a roundtable discussion at an osteoporosis conference in Lausanne , Switzerland , the big vitamin D researchers Vieth, Holick, Heaney, and others agreed that an optimal 25-D blood concentration for most people is 75 to 80 nmol/L. (1 nmol/L = 1 ng/mL x 2.5) This “ideal” is about twice as high as the amount commonly used in studies to mark between low and adequate.
Want to read more about vitamin D? You can certainly read our past newsletters. There is an excellent article in two parts at Science News. Go to:
Here are links to our growing collection of past articles on Vitamin D:
[i] Stroke. 2001 Jul;32(7):1673-7
Vitamin D deficiency and risk of hip fractures among disabled elderly stroke patients.
Sato Y, Asoh T, Kondo I, Satoh K.
Department of Neurology, Kurume University Medical Center , Japan . firstname.lastname@example.org
BACKGROUND AND PURPOSE: Risk of hip fracture after stroke is 2 to 4 times that in a reference population. Osteomalacia is present in some patients with hip fractures in the absence of stroke, while disabled elderly stroke patients occasionally have severe deficiency in serum concentrations of 25-hydroxyvitamin D (25-OHD) (</=5 ng/mL). To determine the effects of vitamin D status on hip fracture risk, we prospectively studied a cohort of patients with hemiplegia after stroke who were aged at least 65 years. METHODS: We compared baseline serum indices of bone metabolism, bone mineral density, and hip fracture occurrence in stroke patients with serum 25-OHD </=25 nmol/L (</=10 ng/mL; deficient group, n=88) with findings in patients from the same cohort who had 25-OHD levels 26 to 50 nmol/L (10 to 20 ng/mL; insufficient group, n=76) or >/=51 nmol/L (>/=21 ng/mL; sufficient group, n=72). RESULTS: Over a 2-year follow-up interval, hip fractures on the paretic side occurred in 7 patients in the deficient group and 1 patient in the insufficient group (P<0.05; hazard ratio=6.5), while no hip fractures occurred in the sufficient group. The 7 hip fracture patients in the deficient group had an osteomalacic 25-OHD level of <5 ng/mL. Higher age and severe immobilization were noted in the deficient group. Serum 25-OHD levels correlated positively with age, Barthel Index, and serum parathyroid hormone. CONCLUSIONS: Elderly disabled stroke patients with serum 25-OHD concentrations </=12 nmol/L (</=5 ng/mL) have an increased risk of hip fracture. Immobilization and advanced age cause severe 25-OHD deficiency and consequent reduction of BMD.
PMID: 11441218 [PubMed - indexed for MEDLINE]
[ii] Poole , K.E., E.A. Warburton, et al . 2005. A contribution to bone loss in hemiplegic stroke patients may be vitamin D deficiency. International Stroke Conference 2005. Feb. 2-4. New Orleans
[iii] Bone. 2004 Apr;34(4):710-5.
Abnormal calcium homeostasis in disabled stroke patients with low 25-hydroxyvitamin D.
Sato Y, Kaji M, Honda Y, Hayashida N, Iwamoto J, Kanoko T, Satoh K.
Department of Neurology, Kurume University Medical Center , Japan . email@example.com
Disabled elderly stroke patients occasionally have very low serum 25-hydroxyvitamin D (25-OHD), which may be due to sunlight deprivation and malnutrition. Many of such patients have very low level of serum 1, 25-dihydroxyvitamin D (1, 25-[OH]2D; calcitriol), and immobilization-induced hypercalcemia may be responsible for inhibition of renal synthesis of calcitriol. To elucidate determinants of serum 1, 25-[OH]2D levels in elderly poststroke patients, we measured serum indices of bone and calcium metabolism and metacarpal bone mineral density (BMD). Patients whose serum 1, 25-[OH]2D concentration was below the mean-3 SD of normal control subjects were defined as the low 1, 25-[OH]2D group and the rest of the patients were designated as the normal group. Mean illness duration was 59 months in the normal group and 20 months in the low group. The Barthel index (BI), which predicts the degree of immobilization, was significantly lower in the low group than in the normal group. Mean serum 1, 25-[OH]2D and 25-OHD concentrations in the normal group were 36.7 pg/ml and 4.4 ng/ml, respectively; and those in the low group were 14.2 pg/ml and 1.8 ng/ml, respectively. Multiple regression analysis identified illness duration and calcium level as independent determinants of 1, 25-[OH]2D in both groups, and PTH in the normal group and 25-OHD in the low group were additional independent determinants. BMD in stroke patients was significantly lower than that in controls, and BMD in the normal group was lower as compared to the low group. BMD correlated negatively with 1, 25-[OH]2D and PTH in the normal group, and hyperparathyroidism may contribute to reduced BMD. These results suggest that treatment of decreased bone mass in stroke patients has to be individualized according to vitamin D status and calcium homeostasis.
PMID: 15050902 [PubMed - indexed for MEDLINE]
[iv] J Clin Invest. 2002 Jul;110(2):229-38
1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.
Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP.
Department of Medicine, University of Chicago , Chicago , Illinois 60637 , USA . firstname.lastname@example.org
Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D(3) injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)(2)D(3) markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)(2)D(3) is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension.
PMID: 12122115 [PubMed - indexed for MEDLINE]
[v] Neurology. 2003 Feb 25;60(4):626-9.
Does compensatory hyperparathyroidism predispose to ischemic stroke?
Sato Y, Kaji M, Metoki N, Satoh K, Iwamoto J.
Department of Rehabilitation Medicine, Institute of Brain Science, Hirosaki University School of Medicine, Japan . email@example.com
BACKGROUND: Parathyroid hormone (PTH) is vasoactive, and the endothelium is one of the target tissues of this hormone. Hyperparathyroidism is frequently associated with hypertension. OBJECTIVE: To determine if hyperparathyroidism, which develops particularly in elderly women as a compensatory mechanism to osteoporosis, may be a risk factor for ischemic stroke. METHODS: Serum PTH levels and bone mineral density (BMD) in 107 elderly patients with ischemic stroke (>or=65 years old) were assessed on the day of onset. The control group consisted of 107 healthy volunteers matched for age and sex. RESULTS: BMD was significantly lower and serum PTH higher in female stroke patients than in control subjects; there was a negative correlation between these two measurements. One-third of the female stroke patients had a serum PTH level higher than the mean + 2 SD of the control subjects (high PTH group), and the interval between menopause and the stroke was significantly longer in the high PTH group than in the normal PTH group. Multiple logistic analyses revealed hypertension and ischemic heart disease were more prevalent in the high PTH group. BMD and PTH were normal in male stroke patients. CONCLUSION: High serum PTH level may be associated with high incidence of ischemic stroke in women, possibly through the increased incidence of hypertension.
[vi] Isr Med Assoc J. 2004 Feb;6(2):82-7
Hypovitaminosis D among inpatients in a sunny country.
Hochwald O, Harman-Boehm I, Castel H.
Department of Pediatrics, Bnei Zion Medical Center , Haifa , Israel . firstname.lastname@example.org
BACKGROUND: Hypovitaminosis D is an important risk factor for osteoporosis and its complications. Previous studies found that the incidence of hypovitaminosis D among patients in an internal medicine ward reached up to 57%. OBJECTIVE: To determine the prevalence and determinants of hypovitaminosis D among patients in internal medicine wards in a sunny country. METHODS: We measured 25-hydroxyvitamin D, parathyroid hormone and various other laboratory parameters, and assessed the amount of sun exposure, dietary vitamin D intake and other risk factors for hypovitaminosis D in 296 internal medicine inpatients admitted consecutively to the Soroka University Medical Center , which is situated in a sunny region of Israel . RESULTS: We found hypovitaminosis D (serum 25-HO-D < 15 ng/ml) in 77 inpatients (26.27%). The amount of sunlight exposure, serum albumin concentration, being housebound or resident of a nursing home, vitamin D intake, ethnic group, cerebrovascular accident and glucocorticoid therapy were all significantly associated with hypovitaminosis D. Multivariate analysis showed a significant association between hypovitaminosis D and Bedouin origin, sun exposure, vitamin D intake, and stroke. Hypovitaminosis D was also found among inpatients who reported consuming more than the recommended daily amount of vitamin D. Parathyroid hormone levels were significantly higher in patients with 25-OH-D levels below 15 ng/ml. In a subgroup of 74 inpatients under 65 years old with no known risk factors for hypovitaminosis D, we found 20.3% with hypovitaminosis D. CONCLUSIONS: Hypovitaminosis D is common in patients hospitalized in internal medicine wards in our region, including patients with no known risk factors for this condition. Based on our findings, we recommend vitamin D supplementation during hospitalization and upon discharge from general internal medicine wards as a primary or secondary preventive measure.
PMID: 14986463 [PubMed - indexed for MEDLINE]