Osteoporosis is marked by loss of bone tissue and low bone mass leading to major physiological changes rendering it porous and brittle. It is a major health concern in developed countries, affecting 30% of women especially during postmenopausal age and 20% of men worldwide.
Healthy bone is a tissue composed of a complex three-dimensional multicellular structure and entails a fine balance between the three major cell types; osteoblasts, osetocytes and osteoclasts which form the fundamental backbone of bone formation.
Osteoblasts are involved in regulating the deposition of bone mineral, the formation of osteocytes and express a variety of signaling molecules that indicate the mature functioning of osteoblasts; and osetoclasts are responsible for bone resorption by absorbing calcium, incorporates the amount needed for bone remodeling and releases the free calcium into the blood.
Osteoporosis is the result of the disruption of this well circuited balance wherein there is a highly active population of osteoclasts causing excessive resorption of calcium that cannot be compensated by mineralising osteoblasts.
In the attempt to bring about an effective clinical strategy for the treatment of osteoporosis, to restore the balance between mineralisation and resorption by drug administration to reduce the osteoclast number, Sujit Kootla and a group of scientists from Uppsala University, Sweden, built a biodegradable drug-polymer complex bisphosphonates (BPs) and hyalauronic acid (HA) to check if the drug has a high affinity to bind to osteoclasts and reduce their number.
This model proved to be a success as, HA enabled the efficient entry of BP, a cornerstone drug treatment for osteoporosis into the cells increasing the toxicity of the drug specifically to ostetoclasts. BP inhibits mature osteoclasts from attaching to the bone surface by altering the cell’s shape thereby slowing down resorption. The polymer-linked drug proved to be a stepping stone to an effective treatment as it is a multimodal vehicle, where BP targets bone and HA targets specific cell surface receptors present on osteoclasts.
This model also demonstrated the preference of the polymer–drug conjugate towards mature osteoclasts and not to other cell types, rendering it as a potential treatment that offers unaffected osteoblasts a chance to re-balance the process of mineralisation and resorption. The team aims to explore in detail the mechanisms involved in signaling of such complexes in cells to better understand the cellular response towards such ‘smart targeting vehicles’, the polymer-drug complex.