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BRIEF REPORT |
1 Hospital del Mar, Unidad de Recerca en Fisiopatología Osea i Articular, Institut d' Investigació Medica, Universidad Autónoma de Barcelona, Barcelona, Spain.
2 Departament de Genètica, Universitat de Barcelona, Spain.
Address correspondence to Dr. Leonardo Mellibovsky, Hospital del Mar, Internal Medicine, Paseo Maritimo 25-27, Barcelona, 08003, Spain. E-mail: lmellibovsky{at}imas.imim.es
A
Osteoporosis is a common disease that affects elderly people. Aging induces loss of bone density and quality resulting in a progressive incidence of fragility fractures. In this study, we report the bone density of one of the oldest men in the world and of several of his first-degree relatives, as well as a genetic screen of these cases. No fractures have been suffered by any of them, and their bone mineral density (BMD) values in terms of z score were normal or lightly decreased. Neither mutations at the longevity-related gene KLOTHO nor the Gly171Val mutation of LRP5 associated with high bone mass was detected in the two centenarian stepbrothers.
Dual-energy x-ray absorptiometry is the main tool for the diagnosis of osteoporosis before fractures occur. However, very few data are available about its value in very elderly persons because of the artifact effect of associated conditions (i.e., osteoarthritis in the spine) and because reference data are scarce in people > 80–85 years old.
The KLOTHO gene has been related to the aging process and to bone mineral density (BMD) (1–6). In contrast, the LRP5 gene has been related to variations in bone mass. In particular, the Gly171Val mutation has been associated with an exceptionally high bone mass phenotype (HBM) (7).
Here we describe the bone mass measured by dual-energy x-ray densitometry, the bone phenotype, and a limited exploratory genetic study of a 113-year-old man and several first-degree relatives, including another centenarian.
METHODS
The group of individuals analyzed is composed of the index case, 113 years old at the time of the study, and four relatives: a stepbrother (101 years old), two daughters (81 and 77 years old), and a nephew (85 years old). BMD was measured by dual-energy x-ray absorptiometry (Lunar DPX–L; Lunar Radiation Corp., Madison, WI), and was expressed in g/cm2, and was measured at the left hip (total hip and femoral neck) and at the lumbar spine (L2–L4). The in vivo precision coefficient of variation of the device was 1.7% at the femoral neck and 1% at the spine. Values of z score were estimated by the formula described by Genant and colleagues (8):
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RESULTS AND DISCUSSION
The index case and most of his relatives were born and live in a small town in Menorca, a Mediterranean island. The index case presented with excellent bone health; there was no kyphosis, and he had never sustained any fracture. He had always been in excellent general health with no history of disease or pharmacological treatments. Until the age of 102 he was actively cycling and working in a family orchard. He was still independent, with an active lifestyle and a vivacious intellect. BMD values for the index case and his relatives are shown in Table 1. Calculated z scores were normal in all the studied members of the family. None of the relatives had ever sustained a fragility fracture.
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Beyond the curiosity of reporting descriptive values in such extremely old people, we would like to emphasize several points. First, T-score classification for the diagnosis of osteoporosis is of limited value in the very elderly population. Besides the common artifacts, reference values taken in a population of 70- to 80-year-olds are at best of dubious applicability; age- and sex-specific reference data are more reliable. Our cases, with no symptoms or any occurrence of fracture, are a clear example.
Second, although a limited genetic screening failed to reveal any contribution of KLOTHO or LRP5, the existence of other longevity and/or high bone mass genes not hitherto described cannot be ruled out.
Finally, besides genetic influences, environmental factors, such as the temperate Mediterranean climate, might be key to the excellent general and bone health in our cases.
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This work was partially funded by grants from the Spanish Ministerio de Sanidad y Consumo (FIS 98/1952), Ministerio de Educación y Ciencia (SAF2004-06085), and the Generalitat de Catalunya (2005SGR 00762 and 00848). M. Bustamante was the recipient of a fellowship from the Spanish Ministerio de Ciencia y Tecnología.
We are sad to announce Joan Riudavets, the index case, passed away during the finalization of this report. We dedicate this work to him and his family, who enthusiastically volunteered for the study.
We also thank Dr. J. Pretus, who encouraged us to perform the study, the Serveis Científico-Tècnics, Universitat de Barcelona, for automated sequencing resources, and M. Pulido for revising the manuscript.
Drs. Mellibovsky and Bustamante contributed equally to this work.
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Decision Editor: Luigi Ferrucci, MD, PhD
Received July 15, 2006
Accepted October 14, 2006
References
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