WHICH ONE IS OSTEOPOROTIC ? HISTAMINE OR HISTAMINE ANTAGONIST ?

WHAT IS ALLERGY?

Allergy is undesirable side effect of immunity which activate in response to allergens (antigen).

MECHANISM OF ACTION OF ALLERGY

Some people have inherited “allergic” tendency which is also known as ATOPIC ALLERGIES because they are caused by a non-ordinary response of the immune system. All atopic allergies are allergic reactions but not all allergies are atopic ones. It is characterized by presence of large quantities of IgE antibodies which is also known as reagins or sensitizing antibodies which is different from common IgG antibodies. On a single mast or basophils cell about half a million IgE antibodies can bind. When an allergen which has multiple binding sites attacks the body binds itself with several IgE antibodies which is already attached to mast or basophils cell then a sequence of reactions occur which ultimately release many substances like histamine, protease, leukotriene, eosinophil chemotactic substances, neutrophils chemotactic substances, heparin and platelet activating factors. Therefore, a number of different types of abnormal tissue responses can occur depending on the type of tissue in which allergen – antibodies reaction occur. 

HOW HISTAMINE WORKS IN OUR BODY?

Histamine works as neurotransmitter in Central nervous system and also have role in regulations of acid secretion. One of the most important functions of histamine is that its act as autacoids (substances which release locally in tissue) and play an important role in immune response of body. In all conditions like Urticaria, Hay fever, hives (swelling) and seasonal allergies histamine play an important role by dilatation of the local blood vessels which increase capillary pressure and increased capillary permeability that will cause fluid leakage in respected tissues results in swelling and there is also attraction of eosinophils and neutrophils to the reactive site in response of antigen-antibodies reaction.

RECEPTORS OF HISTAMINE 

There are 4 types of histamine receptors

H1 RECEPTORS

H1 receptors mediate allergic reactions and expressed themselves on bones also according to some studies. They are also present in Central nervous system. 

H2 RECEPTORS

H2 receptors regulate acid secretion

H3 and H4 are other two histamine receptors. 

EFFECTS OF HISTAMINE ON BONE (H1 RECEPTORS)         

What are the effects of histamine on bones? It is not clear because of limited studies availability but I will discuss it in light of the studies of THE AMERICAN JOURNAL OF MEDICINE. Role of histamine is characterized by Masto cytosis in which due to antigen-reagins (antibodies) reaction histamine is released. Histamine acts as autacoids for metabolism of bone. Increase release of histamine increase the breakdown of bone through osteoclast cells. As a result of it, break down tissue enter into blood or extra-cellular fluid (ECF) that’s mean calcium, phosphorous and other minerals released into blood or ECF. This break down of bone is known as resorption of bone. Due to this resorption, bones become spongy and porous which is known as osteoporosis.

Some studies on mice suggests that deficiency of mast cells results in deficiency of histamine and there is increase in RANKL (osteoclastic differentiation factor) in osteoblast cells (cells responsible for ossifying bone) and bone marrow but RANKL is alone failed to show osteoclastic activity. Histamine and RANKL both of them potentiate osteoclastic effects on bones.

Another factor which studies suggests that decrease histamine level increase serum calcitriol which in turn increase bone formation. Calcitriol also increase RANKL expression in osteoblast cell and bone marrow but unable to show osteoclastic activity because of lack of histamine.   

From this studies, role of histamine receptors antagonists became easier to understand that How increase histamine level show osteoclastic activity and how histamine depletion increase bone mineral density? 

GENERATIONS OF H1 RECEPTORS ANTAGONIST   

H1 receptors antagonists are classified as follow, 

CLASSICAL OR FIRST GENERATIONS H1 RECEPTORS ANTAGONIST

This generation includes Cyproheptadine, Chlorpheniramine, Promethazine and Diphenhydramine. This generation has ability to cross BBB and mediate sedation effects by acting on H1 receptors of CNS (Central nervous system).

SECOND GENERATIONS H1 RECEPTORS ANTAGONIST

This generation includes Astemizole, Cetirizine, Loratadine, Fexofenadine and terfenadine. They are less permeable to CNS and show less or no sedating effects.

HOW H1 RECEPTORS ANTAGONIST PROTECTS BONE

As we already discussed that histamine show osteoclastic activity while H1 receptors antagonist by blocking histamine receptors results in depletion of histamine. Deficiency of histamine exhibits Osteoprotective effects by blocking osteoclastic pathways and showed increase bone mineral density. How the histamine deficiency increased serum cortical level and exhibits osteoblastic activity as all this we discussed above in detailed. We can say that may be due to this Osteoprotective effects of H1 receptors antagonist they were prescribed in elderly patients to protect their bones from osteoporosis.                                  

Another factor of osteo protection may be due to the reason is that allergic reactions cause inflammation and swelling of bones because of increase burden on immunological system. Most of the patients who affected due to seasonal allergies, have also complain of joint pain. H1 receptors antagonist independent of their Osteoprotective effects also reduces inflammation and may be results in decrease swelling of bones beside reduction of inflammation at the reactive tissue site Reduction of inflammation and Osteoprotective effects of antihistamine medicine may be helpful in relieving the joints or bone pain.

HOW LONG THE OSTEOPROTECTIVE EFFECTS OF HISTAMINE RECEPTORS ANTAGONIST WILL LAST? 

In the light of THE AMERICAN JOURNAL OF MEDICINE that Osteoprotective effects of histamine receptors antagonist will not last for more than 6 months. Why? The reason is unclear. 

EFFECTS OF H1 RECEPTORS ANTAGONIST ON THE SKELETAL SYSTEM OF GROWING CHILDREN 

According to one studies H1 receptors antagonist has little but significant effects on rapidly growing mice. If we co- relate this study with growing children and adolescent then the skeletal system of above-mentioned population must be affected due to H1 receptors antagonist because children are most affected population due to seasonal allergies, cold and flu. Prescribing of H1 receptors antagonist is very common in children and long term or chronic use of antihistamine medicine may cause future osteoporosis. 

MOST COMMONLY REPORTED ADVERSE EFFECTS OF H1 RECEPTORS ANTAGONIST

When you have interaction with patients as a pharmacist then large population of female patients aged 40 or more have complaints of joint pain after taking Cetirizine for less than a period of 1 month for seasonal allergies despite the fact that studies show Osteoprotective effects of histamine receptors antagonist. May be due to allergies the swollen ankles or joints are reported. May be due to effects of H1 receptors antagonist or may be due to Osteoprotective effects of antihistamine medicine not lasts for longer period of time OR may be due to age related effect. WHY IT’S HAPPENED? The reason is unclear and require more elaborated data to make more understanding about the role of histamine or histamine antagonist on bones. 

In short, we can’t predict the final opinion because of limited studies and less data. More research is required to establish the facts about the effects of H1 receptors antagonist on bones. The purpose of the article doesn’t mean that stop taking your medicine. If you have faced any joint pain or any adverse effect of medicine consult to your doctor or pharmacist. They will advise you what to do? What prophylaxis medicine (vitamin D and Calcium) will help you for joint pain while you are on H1 receptors antagonist. However, effects of histamine and histamine antagonist on bones is strange. May be in future, extensive research will be helpful for us to understand the role of histamine and their antagonist on bones.