Fresh hope for old bones
Osteoporosis, the disease that weakens bones to the point of fragility and possible fracture, has long been known to be an irreversible condition. But a new study by researchers from institutes in China and Hong Kong provides hope that the debilitating disease could one day be remedied.
The multidisciplinary team of 30 scientists, including those from Hong Kong Baptist University (HKBU) and the China Astronaut Research and Training Centre in Beijing, has identified a type of gene-regulating molecule that acts as a key barrier to bone formation in skeletal disorders.
Further, this molecule could potentially be derived from herbal plants. Published in Nature Scientific Journal last month, the study suggests that therapeutic inhibition of the molecule, called miR-214, may promote bone formation and therefore may reverse osteoporosis. The molecule is a type of microRNA, a small molecule of ribonucleic acid (RNA), which is similar to deoxyribonucleic acid (DNA), the genetic material of a cell.
Scientists estimate that 500 to 1,000 microRNAs exist in the human genome. MicroRNAs play a crucial role in regulating genes, most typically by attaching to a piece of messenger RNA and blocking it from being translated into a protein.
The miR-214 molecule has previously been shown to play a role in cancer tumour progression and metastasis, but this study is the first to report its role in the regulation of bone formation.
Led by Dr Zhang Ge, an Associate Professor at the Institute for Advancing Translational Medicine in Bone & Joint Diseases at HKBU, the research team found that elevated miR-214 levels was linked with a lower degree of bone formation in bone specimens from aged patients with fractures. The team also further defined the role of miR-214 by its capacity to mediate or alter an important protein in bone formation, called ATF4.
"Our observations give the first evidence from clinical bone specimens with low bone mass and osteoporotic fracture that miR-214 inhibits bone formation," Zhang explains. "This study provides a novel target for [the research and development] of a new osteoporosis drug." However, Zhang points out that future studies are not yet ready for trials in humans.
His next step will be to determine the structure of miR-214 for designing new drugs or screening compounds from natural products in herbal plants.
Professor Lu Aiping, dean of the School of Chinese Medicine at HKBU, is optimistic about the team's new finding: "I hope that Dr Zhang's group can further determine the structure of miR-214 so as to design and screen the compounds from Chinese medicinal plants for the discovery of new anti-bone-loss drugs."
Bone is living tissue, and continuously renews and changes through a process called remodelling. There are two distinct stages in the bone remodelling cycle: bone resorption (breakdown) and bone formation.
During resorption, special cells called osteoclasts on the surface of bones dissolve tissue and create small cavities. During formation, osteoblasts fill these cavities with new tissue.
When healthy, bone resorption and formation take place in close sequence and remain balanced. An imbalance in the bone remodelling cycle normally occurs during menopause and with ageing in both genders. An imbalance can result in bone loss that leads to osteoporosis.
Osteoporosis is becoming more prevalent worldwide due to the ageing population. The condition is particularly a problem for postmenopausal women. According to Professor Suzanne Ho Sut-ying, research professor of community and family medicine and head of division of epidemiology of the Jockey Club School of Public Health, osteoporosis is an important public health concern.
There are two categories of osteoporosis medications: antiresorptive medications that slow bone loss and anabolic drugs that increase the rate of bone formation. Osteoporosis medication use and effectiveness depends on the patient characteristics, medical history and preference, says Ho.
She adds: "Further drug development is certainly required. But treatment will still build on the basic requirement of adequate dietary intake, particularly calcium and lifestyle strategy like physical activity and vitamin D exposure."
According to experts, the best strategy for osteoporosis prevention is to develop a strong bone bank when young. This is easily achieved with regular exercise, good nutrition and keeping a healthy lifestyle.
Osteoporosis risk factors
• Being over age 50
• Being female
• Family history
• Low body weight
• Broken bones or height loss
• Not getting enough calcium and vitamin D
• Not eating enough fruits and vegetables
• Getting too much protein, sodium and caffeine
• Having an inactive lifestyle
• Drinking too much alcohol
• Losing weight
From the US National Osteoporosis Foundation