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Does Allergy Break Bones? Osteoporosis and Its Connection to Allergy

Maria Maddalena Sirufo 1 2, Mariano Suppa 3, Lia Ginaldi 1 2, Massimo De Martinis 1 2

DOI: 10.3390/ijms21030712

: Osteoporosis and allergic diseases are important causes of morbidity, and traditionally their coexistence has been attributed to causality, to independent processes, and they were considered unrelated. However, the increasing knowledge in the field of osteoimmunology and an increasing number of epidemiological and biological studies have provided support to a correlation between bone and allergy that share pathways, cells, cytokines and mediators. If the link between allergic pathology and bone alterations appears more subtle, there are conditions such as mastocytosis and hypereosinophilic or hyper-IgE syndromes characterized by the proliferation of cells or hyper-production of molecules that play a key role in allergies, in which this link is at least clinically more evident, and the diseases are accompanied by frank skeletal involvement, offering multiple speculation cues. The pathophysiological connection of allergy and osteoporosis is currently an intriguing area of research. The aim of this review is to summarize and bring together the current knowledge and pursue an opportunity to stimulate further investigation.


In this review, we have summarized and discussed the many factors that link allergies and bone metabolism to give an updated report on this topic . We tried to look through epidemiological, clinical, and laboratory data to highlight these connections. Molecules, cells, diseases, and drugs constitute the diferent perspectives we took to look at this issue.

If the clinical correlation between proliferative pathologies such as mastocytosis or hyper-IgE syndrome and skeletal pathology is historically known, the most recent epidemiological data confirm a link between osteoporosis and pollen-allergy, asthma, atopic dermatitis, urticaria, milk allergy.

Equally certain is the link between bone pathology and therapies adopted in the treatment of diseases with allergic etiology. No longer are steroids alone responsible, but antihistamines, pump inhibitors, antileukotrienics. On the other hand, it is more di_cult to go into an interconnected pathogenetic hypothesis of the two diseases. An inflammatory picture is the fundamental pathogenetic moment for both, and the cellular and humoral protagonists are mostly the same, however it is easy to imagine how di_erent balances and modulations in both cases can be dificult to read and interpret. A leading mediator of allergy, histamine, has been shown to have a role in the determinism of bone pathology, and in the same way vitamin D which has a leading role in bone metabolism afects the modulation of allergic diseases. Mast cells, leading actors of allergic inflammation, produce molecules that afect bone formation and turnover. The signal pathway of NF-kB plays a major role both in allergic inflammation and in regulating bone resorption and it is suggested as a potential therapeutic target [94]. The two Th2 cytokines IL-31 and IL-33 demonstrated to be relevant in the pathogenesis of both allergy and osteoporosis as well as autophagy and these too have been suggested as potential therapeutic target . The role of so many actors may vary and their final efect depends on multiple factors, including their mutual interaction and ultimately the combined action in the diferent phases of inflammation and/or bone remodelling.

While confirming that allergy and bone metabolism have common mediators and pathways, the available data are heterogeneous and sometimes conflicting. A great certainty is that it is a matter of extreme complexity still in an embryonic phase of study that requires further targeted and in-depth studies. The aim of the work was to summarize the current knowledge on the subject to make clinicians aware of the preventive and therapeutic implications and to stimulate researchers on new intriguing hypotheses of study.