WHAT IS ALLERGY?
Allergies are undesirable side effects of immunity that activate in response to allergens (antigens).
WHAT IS ATOPIC ALLERGY?
Some people have an inherited allergic tendency, known as atopic allergies, because it is caused by a non-ordinary response of the immune system. All atopic allergies are allergic reactions, but not all allergies are atopic.
MECHANISM OF ACTION OF ALLERGY
Allergy is characterized by the presence of large quantities of IgE antibodies, also known as reagins or sensitizing antibodies, which differ from common IgG antibodies. On a single mast cell or basophil, about half a million IgE antibodies can bind. When an allergen with multiple binding sites attacks or enters the body, it binds with several IgE antibodies already attached to mast cells or basophils. This initiates a sequence of reactions that ultimately release many substances like protease, leukotrienes, eosinophil chemotactic substances, neutrophil chemotactic substances, heparin, and platelet-activating factors along with histamine.
As a result, different types of abnormal tissue responses can occur depending on the tissue where the allergen-antibody reaction takes place.
ROLE OF HISTAMINE IN OUR BODY
• Histamine works as a neurotransmitter in the central nervous system via H1 and H3 receptors.
• It plays an important role in the regulation of acid secretion, mediated through H2 receptors.
• Histamine acts as an autacoid (a substance released locally in tissue) and plays an essential role in the immune response.
• In allergic conditions like urticaria, hay fever, hives, and seasonal allergies, histamine causes dilation of local blood vessels, increases capillary permeability, leading to fluid leakage and swelling. It also attracts eosinophils and neutrophils to the reactive site.
TYPES OF HISTAMINE RECEPTORS
• H1 Receptors – Mediate allergic reactions and may influence bone metabolism. Also present in the CNS.
• H2 Receptors – Regulate stomach acid secretion.
• H3 Receptors – Involved in neurotransmitter release in the CNS.
• H4 Receptors – Involved in inflammation and are found on immune cells.
EFFECTS OF HISTAMINE ON BONE
• Osteoclast Activity: Histamine, released during allergic reactions, increases bone breakdown via osteoclasts.
• Resorption of Bone: Leads to release of calcium, phosphorus, and minerals into blood.
• Osteoporosis: Chronic bone resorption makes bones spongy and porous.
• RANKL: A factor produced by osteoblasts that binds to RANK receptors on osteoclast precursors. Histamine enhances RANKL effects, increasing bone degradation.
Thus, increased histamine promotes osteoclastic activity, while histamine depletion improves bone mineral density and enhances bone formation.
HISTAMINE ANTAGONISTS (H1 BLOCKERS)
• First Generation: Cyproheptadine, chlorpheniramine, promethazine, diphenhydramine – cross BBB and cause sedation.
• Second Generation: Astemizole, cetirizine, loratadine, fexofenadine, terfenadine – less CNS permeability, minimal sedation.
OSTEOPROTECTIVE EFFECTS OF HISTAMINE ANTAGONISTS
• Blocking H1 receptors depletes histamine, reducing osteoclastic activity and increasing bone mineral density.
• Histamine deficiency increases serum cortical level and promotes bone-forming (osteoblastic) activity.
• May reduce bone inflammation and swelling caused by allergies.
DURATION OF OSTEOPROTECTIVE EFFECT
According to studies in The American Journal of Medicine, osteoprotective effects of H1 antagonists last no more than 6 months. The underlying cause is still unclear.
CONCERNS IN CHILDREN AND ADOLESCENTS
While H1 antagonists are widely used in children for allergies, chronic use may affect the developing skeletal system, increasing the risk of osteoporosis.
PATIENT OBSERVATIONS AND ADVERSE EFFECTS
Some pharmacists note that women over 40 experience joint pain after short-term use of cetirizine. Possible reasons:
• Short-lived osteoprotective effects
• Inflammation from allergic reactions
• Age-related bone changes
FINAL THOUGHTS
Histamine promotes bone loss, while H1 antagonists may offer temporary protection. Long-term impacts, especially in children and older adults, require further study. Calcium and vitamin D supplementation during antihistamine therapy may help support bone health.
References
The American Journal of Medicine: https://www.amjmed.com/
National Institutes of Health – PubMed: https://pubmed.ncbi.nlm.nih.gov/
Histamine & Bone Remodeling Studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC/