Glucocorticoids have historically been an important area in skeletal metabolism, as they can interfere with bone cell activity and the PTH axis – Vitamin D – Calcium.
Since the time of Harvey Cushing it is known that endogenous excess of glucocorticoids causes a severe form of secondary osteoporosis.
Over time glucocorticoids have become almost irreplaceable drugs in rheumatological, pneumological, gastroenterological, dermatological, hematological fields and, more recently, in organ transplantation.
Their widespread use, often for long periods and at high doses is also known to be the cause of severe osteoporosis.
Many other hormones in addition to glucocorticoids are able to significantly interfere with skeletal metabolism, including thyroid hormones, prolactin and of course gonadic hormones, PTH and GH and IGF1. Excess and/or defect of such hormones is often the cause of secondary osteoporosis.
The incidence of secondary osteoporosis is different in the two sexes: in males, 30 – 60% of osteoporosis cases are attributable to secondary causes, in females during infertile age secondary causes represent more than 50% of cases.
Thyroid hormones accelerate bone turnover and shorten the normal bone remodeling cycle. Although both osteoblastic and osteoclastic activity have increased, the latter predominates and the end result is bone loss. Hyperthyroidism of any given cause is therefore a risk factor for osteoporosis and fractures including thyroxine therapy at suppressive doses (TSH less than 0.1 mIU / L) that is commonly used to inhibit the progression or recurrence of thyroid cancer (papillary or follicular).
Sex steroids (estrogens, progestins and androgens) play an important role in skeletal homeostasis in all hypogonadal states. Post-menopausal osteoporosis is the main form of primary osteoporosis with the lack of estrogens being responsible for hyperactivation of osteoclast and bone resorption. Due to its huge impact in quality of life and survival linked to increased risk of fractures, clinical research and practice are striving for always more effective treatment options. Hypoestrogenism causes also secondary osteoporosis with pathogenetic mechanisms similar to those of post-menopausal osteoporosis. Some clinical conditions of endocrinological interest likeTurner syndrome, Klinefelter syndrome, Nervous anorexia, Hypothalamic amenorrhea, Hyperprolactinemic amenorrheaare associated with an increased risk of osteoporosis and fractures.
Androgens play an important role at the bone level, the effect is largely attributable to their conversion into estrogen by the “aromatase” enzyme.
Androgen deficiency is associated in males with reduced bone density and an increased risk of fracture, especially at the femur.This type of secondary osteoporosis today assumes great clinical importance due to widely used treatment with GnRH and with other various molecules with anti-androgenic action in subjects suffering from advanced prostate cancer that determine a marked reduction of testosterone and induces a rapid and progressive depletion of bone mass.
Parathyroid hormone (PTH) increases bone turnover and its effects on bone can be catabolic. Primary hyperparathyroidism (due to glandular hyperplasia or adenoma) is a relatively frequent condition with an incidence between 1/500 to 1/1000 (in adults over 50-60 years), with a peak between 40 and 65 years and a female / male ratio of approximately 3:1.The asymptomatic forms – since the determination of calcium has become routine – are still predominant (more than 80%)
The clinical picture is characterized by a demineralization of the skeletal system especially in the cortical bone, in particular at the level of distal phalanges, 3rd distal radius, clavicles and skull, up to the most advanced pictures of fibrous-cystic osteopathy generalized (Von Recklinghausen’s disease).
Bone pain, pathological fractures, kidney lesions (nephrolithiasis) and a metabolic syndrome with changes in phospho-calcium balance are clinical manifestations of the disease. Enormous interest has been raised in the last decade by possible skeletal involvement also in hypoparathyroidism also in the light of new treatment perspectives.
Growth hormone (GH) plays a significant role on bone metabolism in the child, favoring enchondral apposition, in the post-pubertal age, allowing the achievement of peak bone mass, and in adults, by increasing bone formation. Some evidences shown that patients aged 55 or younger with adult GHD have reduced BMD values with an increased prevalence of osteoporosis and fractures that are two to three times higher than the reference population.GH replacement treatment of adults with GHD induces significant effects on markers of bone formation and resorption suggesting an increase in bone turnover. Growth hormone excess from a pituitary adenoma as well as ACTH, prolactin and TSH hypersecretion are emerging causes of increase skeletal fragility and the seminal discoveries in the last two decades have led to a new subdiscipline of the pituitary and bone field called bone neuroendocrinology.
GIOSEG initiatives started almost 30 years ago in 1991 with the creation of GISGO a study group focused on glucocorticoid-induced osteoporosis led by a visionary scientist and clinician Prof. Alberto Angeli from Turin (Italy) who is the co-founder of GIOSEG. Prof. Angeli was able to anticipate the international bone community in the understanding of lack of awareness, diagnosis and adequate treatment of one of the most serious forms of osteoporosis as that caused by the widespread administration for multiple diseases of pharmacological doses of glucocorticoids. The multidisciplinary nature of the management of glucocorticoid induced osteoporosis including the many non bone specialists using glucocorticoid treatment was one of the pillars of the GISGO study group which was able to produce several high quality international meetings (the very well known GIO meeting series) and papers setting the state of the art recommendations for the diagnosis and treatment of steroid induced osteoporosis. GISGO was able also to raise the awareness for GIO at the levels of Institutions with the ultimate goal to achieve for all patients treated with steroids in the world an adequate level of protection for their bones.
With the increased awareness for the role of hormones and endocrine diseases in the pathophysiology of skeletal fragility and fractures it was decided that focusing only on glucocorticoids was no more reflecting the huge development in the field of skeletal endocrinology. Therefore, GISGO gave birth to GIOSEG, the glucocorticoid induced skeletal endocrinology group which now can count on more than 300 members from Italy (and other part of the world) and a strong International Advisory Board. The purpose of GIOSEG is to increase the awareness, the early diagnosis and improve treatment of all those forms of osteoporosis linked to hormonal derangements. As per its bylaws GIOSEG promotes scientific meetings(the world wide known Skeletal Endocrinology series) gathering the greatest experts in the field from the basic and clinical perspective. GIOSEG is also advocating at institutional levels for adequate treatment of osteoporosis and equal opportunities for all citizens to have access to bone protective diagnosis and treatment with scientific publications, statements for specialists and educational initiatives for young in training doctors, non specialists and lay public with the final aim to fight also in collaboration with other international groups, the plague of osteoporosis as a social but yet underdiagnosed and undertreated disease highly costly for the community.