Therapeutic Implications Fig. 1 International comparison of serum 25(OH)D measurements in three European and two US laboratories. The points represent individual values of serum 25(OH)D measured by four laboratories in eight serum samples and by two laboratories in seven other serum samples. [Reproduced with permission from P. Lips et al.: Osteoporos Int 9:394–397, 1999 (28). © International Osteoporosis Foundation and National Osteoporosis Foundation.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 2 Serum vitamin D<sub>3</sub> concentration after total body exposure to artificial sunlight (UV 260–360 nm) in six white young adults (20–30 yr) and six white elderly people (62–80 yr) with skin type III. Serum vitamin D<sub>3</sub> concentration was measured for 7 d. The area under the curve for serum vitamin D<sub>3</sub> suggests that the production of vitamin D<sub>3</sub> in the skin in the elderly is about 25% of that in young adults.[ Reproduced with permission from M. F. Holick et al.:Lancet 2:1104–1105, 1989 (35). © The Lancet Ltd.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 3 Mean values of serum 25(OH)D from the studies in Table 1 according to geographical region (Fig. 3A) or to subject/patient/residence category (Fig. 3B). Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 4 Serum 25(OH)D (median, 5th-95th percentile) in 250 healthy adults (blood donors), 74 independent elderly subjects, 142 institutionalized elderly patients, and 125 patients with hip fracture. The samples in all groups were collected throughout the year. All measurements were performed by HPLC followed by competitive protein binding assay (data from Refs. 37, 56, 85). [Reproduced with permission from M. E. Ooms: Thesis. Vrije Universiteit Amsterdam, 1994 (105).] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 5 Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Study. The points represent the mean values of each center for males and females according to northern latitude. The lowest values were found in Greece, Spain, and Italy. [Reproduced with permission from R. P. J. Van der Wielen et al.: Lancet 346:207–210, 1995 (45). © The Lancet Ltd.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 6 A, Negative relationship between serum PTH and serum 25(OH)D in 330 elderly women (>70 yr) in Amsterdam. The best fit was obtained by a linear regression model with a threshold for serum 25(OH)D at 25 nmol/liter with a negative correlation below the threshold (P = 0.02) and no significant correlation above the threshold. B, Negative relationship between serum PTH and serum 25(OH)D in 1,569 adults (50 ± 6 yr) from the SUVIMAX study. The best fit was obtained by nonlinear regression analysis (P < 0.01). A plateau for serum PTH was reached at serum 25(OH)D above 78 nmol/liter. Below this level, serum PTH started to rise. [Panel A reproduced with permission from M. E. Ooms: Thesis. Vrije Universiteit Amsterdam, 1994 (105); panel B reproduced with permission from M. C. Chapuy et al.: Osteoporos Int 7:439–443 1997 (10). © International Osteoporosis Foundation and National Osteoporosis Foundation.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 7 Relationship between serum 25(OH)D and BMD of the femoral neck in 330 elderly women. The best fit was obtained by a linear regression model with a threshold for serum 25(OH)D at 30 nmol/liter. The correlation was significant (P < 0.001) when serum 25(OH)D < 30 nmol/liter. With higher values of serum 25(OH)D, the correlation with BMD was no longer significant.[ Reproduced from M. E. Ooms et al.: J Bone Miner Res 10:1177–1184, 1995 (57) with permission from the American Society for Bone and Mineral Research.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 8 Relationship between the half-life of <sup>3</sup>H-25(OH)D and the serum 1,25-(OH)<sub>2</sub>D concentration in 49 patients shown as the regression line and 95% confidence limits. Correlation coefficient r =− 0.63, P < 0.001. The data are from patients after gastrectomy (O), patients with primary hyperparathyroidism before and after surgery (□), and patients with other disorders of bone and mineral metabolism (Δ). When serum 1,25-(OH)<sub>2</sub>D is high, the half-life of 25(OH)D is short, indicating an increased catabolism that may aggravate vitamin D deficiency. [Reproduced with permission from M. Davies et al.: J Clin Endocrinol Metab 82:209–212, 1997 (87) © The Endocrine Society.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 9 Schematic presentation of pathways from vitamin D deficiency and secondary hyperparathyroidism to osteoporotic fractures. Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 10 Response of serum 25(OH)D to UV irradiation (UVB, half of the minimal erythematous dose, 3 times per week) on 1,000 cm<sup>2</sup> of the back of elderly women with vitamin D deficiency in comparison with the response to oral vitamin D<sub>3</sub> 400 IU/d (vit D) and a control group (control). The study included 45 psycho-geriatric patients randomized in three groups. Data are expressed as median, 25th-75th percentile. [Reproduced from V. G. M. Chel et al. : J Bone Miner Res 13:1238–1242, 1998 (36) with permission of the American Society for Bone and Mineral Research.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 11 Effect of vitamin D<sub>3</sub> 400 IU/d in residents of apartment houses or homes for the elderly on bone loss in the femoral neck and trochanter. The difference in mean change (%) between the vitamin D and the placebo group is shown in the first year, second year, and total period. The se is indicated by error bars. * P < 0.05; ** P < 0.01. [Reproduced with permission from M. E. Ooms et al.: J Clin Endocrinol Metab 80:1052–1058, 1995 (186). © The Endocrine Society.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society
Therapeutic Implications Fig. 12 Effect of vitamin D<sub>3</sub>, 800 IU/d, and calcium, 1,200 mg/d, vs. double placebo on the incidence of hip fractures and other nonvertebral fractures in 3,270 French nursing home residents. The effect is presented as cumulative probability of fracture in the placebo group (□) and the group treated with vitamin D<sub>3</sub> and calcium (•), estimated by the life-table method and based on the length of time to the first fracture. The decrease was significant after 1.5 yr. [Reproduced with permission from M. C. Chapuy et al.: N Engl J Med 327:1637–1642, 1992 (187). © 1992 Massachusetts Medical Society. All rights reserved.] Therapeutic Implications Endocr Rev. 2001;22(4):477-501. doi:10.1210/edrv.22.4.0437 Endocr Rev | Copyright © 2001 by The Endocrine Society