359 Review ISSN 1758-4272 10.2217/IJR.11.24 © 2011 Future Medicine Ltd Int. J. Clin. Rheumatol. (2011) 6(3), 359–369 Age- and gender-related macro- and micro-architecture changes in bone structure and implications for treatment Bone strength, which is resistance to fracture, depends not only on the bone mass, but also on its spatial distribution (micro- and macroarchi- tecture) and the intrinsic properties of the mate- rials that constitute the bone [1] . A particular fea- ture of the bone is the ability to adapt its size and shape in response to mechanical loads, through the process of modeling achieved by the inde- pendent action of osteoblasts and osteoclasts. Modeling occurs principally during growth, but also in the adult, according to Wolff’s law, in response to a mechanical load, as the use of a certain limb in a sport player, resulting in a thickening of bone cortex and an enlargement of external bone diameter, or conversely to the unloading of the skeleton, as during bed rest or space flight [2,3] . Another process, known as remodeling, allows the skeleton to maintain mechanical integrity through the constant osteoclastic resorption of damaged bone followed by osteoblast-mediated deposition and mineralization of new matrix. Overall remodeling rates average 8–10% per year in the adult [3] , but individual bone sites can vary widely depending on the level of accumulated microdamage. At a macroscopic level, two types of bone can be distinguished: the cortical bone, located in the shaft of long bones and on outer surfaces of the flat bones, and the trabecular bone, found at the extremity of long bones and at the inner parts of flat bones. The two compartments differ for micro- and macro-architecture and speed of turnover. Bone loss starts at the bone surfaces; therefore, changes in bone mass occur earlier and more intensively in trabecular bone than in cortical [3] . When bone remodeling is unbalanced Sex hormones influence bone remodeling: in the elderly, with decreasing of estrogen and testos- terone, bone resorption exceeds bone formation, resulting in a loss of bone mass. Osteoporosis, the most common metabolic bone disease, characterized by low BMD and microarchitectural deterioration of bone tis- sue, with a consequent increase in the suscet- tibility to fragility fractures, has become an increasingly important public health problem due to the rapidly aging population. Currently every third postmenopausal woman and every fifth man older than 50 years suffer from osteoporosis [4] . It is important to identify the possible patho- logical mechanisms underlying bone fragility in old age; in particular, it is of interest to con- sider sexual dimorphism in age-related skel- etal changes, which is reflected in the gender differences in bone fracture rates [5] .  Age-related bone structure changes in men & women The age-related changes underlying the increase in skeletal fragility include bone min- eral loss by trabecular resorption, endocortical Bone is a dynamic tissue, which has the ability to adapt its shape and size in response to mechanical loads through the modeling process, and to be constantly renewed by remodeling. These processes are influenced by genetic, hormonal and lifestyle factors. Age-related variation in bone strength, which depends both on bone density and bone structure, are gender-specific, and this explains the difference in the incidence of osteoporotic fractures at specific sites between men and women. Even though estrogen deficiency is more pronounced in women, it appears to be one of the major causes of osteoporosis in both genders. Most of the drugs used to treat osteoporosis have been tested on postmenopausal women; nevertheless, some drugs have been shown to be effective also in men. An accurate examination of the medical history of the patient, possibly with the aid of radiological and advanced techniques to image bone quality should direct the physician in selecting the most appropriate therapy. KEYWORDS: aging  biphosphonates  bone macro- and micro-architecture  bone strength  osteoporosis  parathyroid hormone  strontium ranelate Loredana Cavalli 1 & Maria Luisa Brandi †1 1 Mineral & Bone Metabolism Disease Unit, Department of Internal Medicine, University of Florence, Italy † Author for correspondence: Tel.: +39 055 794 6303 m.brandi@dmi.unii.it For reprint orders, please contact: reprints@futuremedicine.com