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Low Vitamin D Status, High Bone Turnover, and Bone Fractures in Centenarians

Department of Internal Medicine and Biomedical Sciences (G.Pa., R.V., P.S., M.Pa., R.D., M.Pe.), University of Parma, 43100 Parma, Italy; Department of Experimental Pathology (G.Pi., C.F.), University of Bologna, 40126 Bologna, Italy; Italian National Research Center for Aging (C.F.), 60121 Ancona, Italy; Department of Biomedical Sciences (L.T.), University of Modena, 41100 Modena, Italy; and Department of Statistical Sciences (P.G.), University of Bologna, 40126 Bologna, Italy

Address all correspondence and requests for reprints to: Giovanni Passeri, M.D., Department of Internal Medicine and Biomedical Sciences, University of Parma, Via Gramsci 14, 43100 Parma, Italy. E-mail: gpasseri{at}unipr.it.

The oldest olds, including centenarians, are increasing worldwide and, in the near future, will represent a consistent part of the population. We have studied bone status and metabolism in 104 subjects over 98 yr of age to evaluate possible interventions able to avoid fragility fractures and disability. Ninety females and 14 males not affected by any acute disease were considered. After a complete clinical assessment, blood was drawn for evaluating bone turnover markers, and performance tests together with skeletal ultrasonography (either at the phalanges or at the heel) were performed. We found that 38 subjects had sustained a total of 55 fractures throughout their lives, and 75% of these were fragility fractures. Twenty-eight fractures occurred at the proximal femur, with 14 after the age of 94 yr. Serum 25-hydroxyvitamin D was undetectable in 99 of 104 centenarians. PTH and serum C-terminal fragment of collagen type I were elevated in 64 and 90% of centenarians, respectively, with a trend toward hypocalcemia. Bone alkaline phosphatase levels were close to the upper limit. Serum IL-6 was elevated in 81% of centenarians and was positively correlated with PTH and negatively correlated with serum calcium. Serum creatinine was not correlated with PTH. Bone ultrasonography showed that most centenarians had low values, and ultrasonographic parameters were correlated with resorption markers. We conclude that the extreme decades of life are characterized by a pathophysiological sequence of events linking vitamin D deficiency, low serum calcium, and secondary hyperparathyroidism with an increase in bone resorption and severe osteopenia. These data offer a rationale for the possible prevention of elevated bone turnover, bone loss, and consequently the reduction of osteoporotic fractures and fracture-induced disability in the oldest olds through the supplementation with calcium and vitamin D.

This study was supported by grants from the Italian Ministry of Health Marcatori molecolari predittivi di Osteoporosi: dalla clinica alla biologia molecolare; Foundation Cassa di Risparmio of Parma e Piacenza; and Foundation Cassa di Risparmio of Verona, Vicenza, Belluno ed Ancona.

Abbreviations: ALT, Alanine aminotransferase; AST, aspartate aminotransferase; GT, -glutamyl transferase; MMSE, Mini-Mental State Examination; 25-OH vitamin D, 25-hydroxyvitamin D; QUI, quantitative ultrasound index; S-CTX, serum C-terminal fragment of collagen type I; SoS, speed of sound; UBPI, ultrasound bone profile index.

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