How to select the doses of vitamin D in the management of osteoporosis

The dose of vitamin D in the management of osteoporosis should be no less than 700–800 IU per day. An optimal dose of vitamin D should raise serum concentrations of 25(OH)D to the desirable range of at least 75 nmol/l. Higher intermittent oral doses of vitamin D may overcome low adherence. Vitamin D supplementation in the management of osteoporosis holds a significant public health potential because of its low cost, excellent tolerability, and combined musculo-skeletal benefits. Fall and fracture prevention with vitamin D is especially appealing in the treatment of older individuals at risk for fall-related fractures. However, bone density, strength, and function benefits with vitamin D include active and inactive subgroups of community-dwelling older men and women. Based on a recent expert panel and supportive evidence presented in this review, serum concentrations of at least 75 nmol/l 25(OH)D will be referred to as desirable. Today, desirable serum 25(OH)D levels of at least 75 nmol/l may only be reached in about one third of US older individuals and even fewer European older individuals. Two main factors discussed in this review may help public health efforts to ensure desirable vitamin D levels for fall and fracture prevention, including (1) a sufficient dose of vitamin D and (2) improved adherence to supplementation.     

Severe vitamin D deficiency in Swiss hip fracture patients

BACKGROUND: Most clinical guidelines for the prevention of hip fractures recommend 800 IU vitamin D per day. This dose shifted serum 25-hydroxyvitamin D levels (25(OH)D) in previous studies to between 60 and 100 nmol/l. AIM: To measure 25(OH)D levels and prevalence of vitamin D supplementation in individuals age 65+ with acute hip fracture. METHODS: 222 consecutive hip fracture patients were investigated over a 12 month period. Mean age of patients was 86 years and 77% were women. RESULTS: Mean serum 25(OH)D levels were low among hip fracture patients admitted from home (34.6 nmol/l), from assisted living (27.7 nmol/l), and from nursing homes (24 nmol/l). Severe vitamin D deficiency below 30 nmol/l was present in 60%, 80% were below 50 nmol/l, and less than 4% reached desirable levels of at least 75 nmol/l. Consistently, only 10% of hip fracture patients had any vitamin D supplementation on admission to acute care with significantly higher 25(OH)D levels among individuals supplemented with 800-880 IU/day (63.5 nmol/l). Controlling for age and gender, vitamin D supplementation, type of dwelling, and season were independently and significantly associated with 25(OH)D levels. CONCLUSION: These data provide evidence that current guidelines for the prevention of hip fractures need further effort to be translated into clinical practice.     

Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.     

Optimal Serum Concentration of 25-Hydroxyvitamin D for Bone Health in Older Korean Adults

Optimal vitamin D concentrations for bone health have not been determined in the Korean population. The aim of this study was to define serum 25-hydroxyvitamin D (25[OH]D) concentrations that indicate insufficiency among older Korean adults as measured by serum intact parathyroid hormone (iPTH) concentrations and bone mineral density (BMD). We analyzed data from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-3), which was conducted in Korea in 2009. We enrolled 1,451 men and 1,870 women aged 49 years and above. After adjusting for variables that could potentially affect serum 25(OH)D concentrations, we found that serum iPTH concentrations began to increase at serum 25(OH)D concentrations below 12.1 ng/mL (30.2 nmol/L). In addition, total-femur BMD increased until serum 25(OH)D concentrations dropped below 20.4 ng/mL (50.9 nmol/L); no significant changes were observed thereafter. Assuming that serum 25(OH)D concentrations below 12.1 and 20.4 ng/mL represent vitamin D insufficiency, the prevalences of vitamin D insufficiency were 8.7 and 50.4 % in men and 17.9 and 66.3 % in women, respectively. Serum 25(OH)D cutoff values of 12.1 ng/mL (OR = 1.26) and 20.4 ng/mL (OR = 1.54) were associated with osteoporosis (P < 0.01); osteoporosis was not associated with a 25(OH)D cutoff value of 30 ng/mL (75.0 nmol/L). In conclusion, serum 25(OH)D concentrations of 20 ng/mL might be sufficient for bone health in older Korean adults.     

Half of the patients with an acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland

Vitamin D deficiency may be one important contributing risk factor for an osteoporotic fracture among elderly. We analyzed serum 25-hydroxyvitamin D [S-25(OH)D] status in patients with an acute hip fracture in southeastern Finland (61°N). Consecutive patients with a fresh hip fracture ( n =223) in two Finnish hospitals during 12 months and 15 months were registered prospectively. S-25(OH)D concentrations (nmol/l) were measured by radioimmunoassay-method. Hypovitaminosis D was defined as S-25(OH)D <37.5 nmol/l and severe hypovitaminosis D:<20 nmol/l. The highest threshold of S-25(OH)D in our analysis was >74 nmol/l. The seasonal variation in S-25(OH)D concentrations was followed. Hypovitaminosis D was found in 53% of the patients. In 9% hypovitaminosis D was severe. Half (50%) of the patients living in their own homes, 55% of those in residential homes, and 61% of institutionalized elderly had hypovitaminosis D. Patients who used both vitamin D and calcium supplement had S-25(OH)D levels between 37.5 nmol/l and 74 nmol/l and >74 nmol/l more often than non-users ( Wx =3.85, p =0.0001). Most (41/61) of the patients who sustained the fracture during the late summer months had S-25(OH)D concentration 37.5 nmol/l, whereas, in winter months the situation was quite the opposite (24/67) ( Wx =3.42, p =0.0006). Twenty-two percent (50/223) had S-25(OH)D concentration >50 nmol/l and four patients >78 nmol/l. Half of the patients with a hip fracture suffered from hypovitaminosis D. The situation was worst in institutional and residential care, although there are personnel for taking care of vitamin D supplementation. In the late summer, one-third and in late winter two-thirds of the patients suffered from hypovitaminosis D. The geographical location of Finland indicates extensive efforts to increase the use of vitamin D supplements among elderly.     

High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency

ObjectivesRecent large trials indicate that adherence associated with a daily regimen of vitamin D is low and limits anti-fracture efficacy with vitamin D supplementation. The aim of this report is to describe changes of 25-hydroxyvitamin D (25(OH)D) serum concentrations achieved with a single oral dose of 300 000 IU vitamin D3.MethodsOver a course of 4 months, we identified 33 elderly with severe vitamin D deficiency (25(OH)D < 25 nmol/l) on admission to acute care. Patients were admitted for musculoskeletal pain, bone disease, or gait abnormalities. The mean age was 80.5 years (SD ± 6.1). All patients were treated with a single oral dose of 300 000 IU D3 in combination with 500–1000 mg calcium supplements per day depending on their dietary calcium intake.ResultsBaseline mean 25(OH)D serum concentrations were 15 nmol/l (SD ± 5.5). Mean 25(OH)D serum concentrations increased to 81.4 nmol/l (SD ± 29.7) at 3 months (29 patients) and were still 69.0 nmol/l (SD ± 17.9) at 6 months (26 patients). Mean serum calcium levels were 2.24 mmol/l (SD ± 0.11) at baseline, 2.28 mmol/l (SD ± 0.18) at 3 months, and 2.28 mmol/l (SD ± 0.13) at 6 months. Two patients with mild hypercalcemia (2.69 mmol/l) at 3 months had normal values at 6 months.ConclusionBased on our observations, a single oral dose of 300 000 IU vitamin D3 raises mean 25(OH)D serum concentrations to the target mean of above 75 nmol/l at 3 months and a mean level of 69 nmol/l at 6 months. As calcium absorption is enhanced with higher 25(OH)D serum concentrations, calcium supplementation may need downward adjustment with this regimen to avoid mild hypercalcemia.     

Correction of preoperative vitamin D deficiency after Roux-en-Y gastric bypass surgery

BACKGROUND: To evaluate the adequacy of supplementation to correct preoperative vitamin D deficiency in adult patients during the year after Roux-en-Y gastric bypass (RYGB) surgery. METHODS: The medical records were reviewed and the preoperative and 12-month postoperative serum 25-hydroxyvitamin D [25(OH)D] levels were compared in patients who underwent RYGB from 2002 to 2004. The serum 25(OH)D levels were defined as being optimal (> or = 80 nmol/L), suboptimal (50-79 nmol/L), or deficient (<50 nmol/L). Patients with deficient 25(OH)D levels were prescribed 50,000 IU ergocalciferol weekly. The remaining patients averaged 710 IU supplemental vitamin D intake daily. RESULTS: The mean patient age was 43.8 +/- 10.7 years, and the mean preoperative body mass index was 51.8 +/- 9.8 kg/m2. Of the 95 patients with baseline and 12-month 25(OH)D levels, 89% were women. The mean preoperative 25(OH)D level was 49.7 +/- 26.5 nmol/L; 34% had suboptimal 25(OH)D levels and 54% had deficient levels before surgery. Twelve months after surgery, those receiving 50,000 IU weekly (n = 40) had a mean 25(OH)D level of 69.2 +/- 22.2 nmol/L; 63% had suboptimal and 8% deficient levels. Those taking 710 IU daily (n = 55) had a mean 25(OH)D level of 85.5 +/- 33.0 nmol/L; 44% had suboptimal and 6% deficient levels. CONCLUSION: Vitamin D deficiency is prevalent in RYGB patients before surgery. The vitamin D status improved markedly after RYGB surgery with either 710 IU vitamin D daily or 50,000 IU weekly. Current supplementation practices do not appear to optimize the serum 25(OH)D levels and need to be more closely examined.     

Bone mineralization defects and vitamin D deficiency: Histomorphometric analysis of iliac crest bone biopsies and circulating 25‐hydroxyvitamin D in 675 patients

Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25‐Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency therefore would be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals, excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters, including osteoid indices, were quantified using the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels were measured for all patients. Statistical analysis was performed by Student's t test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15% of the analyzed patients presented with an osteoid surface per bone surface (OS/BS) of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in osteoid volume per bone volume (OV/BV) greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of bone volume per trabecular volume (BV/TV) throughout all ages and affected both sexes equally. While we could not establish a minimum 25(OH)D level that was inevitably associated with mineralization defects, we did not find pathologic accumulation of osteoid in any patient with circulating 25(OH)D above 75 nmol/L. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25(OH)D below 75 nmol/L and strongly argue that in conjunction with a sufficient calcium intake, the dose of vitamin D supplementation should ensure that circulating levels of 25(OH)D reach this minimum threshold (75 nmol/L or 30 ng/mL) to maintain skeletal health. © 2010 American Society for Bone and Mineral Research     

Vitamin D deficiency in the elderly in Athens,Greece

Vitamin D deficiency characterized by low 25-hydroxyvitamin D [25(OH)D] levels has been found to be prevalent among the elderly in many regions of the world. To investigate the vitamin status in elderly community-living persons in Athens, we measured 25(OH)D and parathyroid hormone (PTH) in elderly persons and young blood donors during the winter and summer. The changes in these parameters in a subgroup of the elderly were studied longitudinally. The blood donors had mean 25(OH)D levels similar in winter and summer and twice as high in winter compared to the elderly. At the end of the winter, about 20% of the elderly had severe vitamin D deficiency, with 25(OH)D below 25 nmol/l, and only 6.5% could be judged as vitamin D sufficient with values above 80 nmol/l. The situation improved during summer, although 64.8% of the elderly continued to have levels below 80 nmol/l. Mean plasma PTH in the elderly in summer was not different from that of blood donors; however, it was doubled during the winter. Regression of PTH on 25(OH)D demonstrated that PTH starts to rise when 25(OH)D falls below approximately 80 nmol/l. We conclude that severe vitamin deficiency associated with secondary hyperparathyroidism is not uncommon in the elderly in Athens during the winter; it subsides during summer, although only one-third of the elderly population attain vitamin D sufficiency during summer. We found that a threshold value of 25(OH)D exists at approximately 80 nmol/l, below which secondary hyperparathyroidism ensues, as described previously.     

Vitamin D Status During Puberty in French Healthy Male Adolescents

The vitamin D status was determined on one to four occasions either after summer (September–October) or after winter (March–April) in 175 male adolescents (13–17 years), resulting in 394 measurements of serum 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH). The subjects lived in a rural area to the north of Paris (49° N). After summer the 25(OH)D concentration was 58.5 ± 18.0 nmol/l (mean ± SD), while after winter it had fallen to 20.6 ±6.0 nmol/l (p= 0.0001). Meanwhile the iPTH concentration was 2.76 ± 0.97 pmol/l (mean ± SD) after summer and increased to 4.20 ± 1.21 pmol/l after winter (p= 0.0001). All the results were pooled and a nonlinear population model with random parameters was used to describe the relationship between serum iPTH and 25(OH)D. When the concentration of 25(OH)D was higher than 83 nmol/l, an iPTH mean ‘plateau’ level at 2.48 pmol/l was reached. When 25(OH)D concentrations fell below 83 nmol/l, the increase in iPTH concentration accelerates, and when the mean 25(OH)D concentration was equal to or lower than 10 nmol/l the mean iPTH level (4.97 pmol/l) was twice as high as the ‘plateau’ value. Received: 26 November 1998 / Accepted: 15 February 1999