Ageing is associated with many degenerative processes, including the gradual deterioration of the skeleton. Osteoporosis (brittle bone) is a common bone disease characterized by bone weakness and an increased risk of fractures that increases dramatically in incidence with age. The risk of osteoporosis and related fractures is determined by a balance between levels of peak bone mass achieved during skeletal growth in adulthood, and the amount of bone that is lost later on in life.
Osteoporotic fractures develop gradually over several years, and they are only diagnosed after the patient experiences a minor fall or sudden impact. In the clinic, osteoporosis and fracture risk are assessed by dual X-ray absorptiometry (DEXA).
Although DEXA remains the gold standard, it has its limitations. In the search for better tools to diagnose osteoporosis, monitor osteoporotic treatments over time and estimate fracture risk, attention has been focused on bone scanning and imaging technologies.
We have recently published our attempts to develop a simple, nail test to detect bone loss associated with osteoporosis in female rats.
Nailing Down Osteoporosis
The decline in estrogen level in women after the menopause triggers changes in the chemical and structural composition of bone. These changes often are the major cause of excessive loss in bone mineral density and content and deterioration in bone quality in osteoporotic patients.
To validate the nail test, we surgically induced osteoporosis in female rats by removing the ovaries and we measured the changes in the protein content of bone and claws (nails) using an optical technique called Raman spectroscopy. This technique is commonly used in forensics to sensitively and non-invasively measures changes in chemical composition and provides a fingerprint by which molecules can be identified.
Additionally, we monitored bone loss in the skeleton by micro-computed topography, a high-resolution, sensitive imaging technique for monitoring the progression of bone growth and bone loss in laboratory animals.
Our results demonstrated that the Raman spectroscopy signature of the fibrous protein keratin in the rat claws predicts the changes in the bone matrix protein collagen and bone loss in osteoporotic rats, with both tissues showing a decrease in how ordered the protein structures are after removal of the ovaries.
A concurrent clinical study has found that the same technology – when combined with clinical risk factors and DEXA data – enhanced the ability to differentiate between postmenopausal women who had suffered a fracture or not.
When combined with previous studies, these findings suggest a potential clinical implication on predicting osteoporotic fractures and monitoring bone-preserving treatments by measuring the level of nail keratin as a surrogate marker for loss in the bone protein collagen.
Due to the use of a simple nail clipping analyzed remotely, such test could also offer patients with the added benefit in reducing possible radiation risks associated with traditional scanning techniques such as DEXA.
It is important, however, to note that, while our recent findings are encouraging, the nail test described needs to go through another wave of studies in other models of age-related osteoporosis and in patients to find the optimal way to exploit this exciting technology in a clinical setting.
Potential As A Bone Metastasis-screening Test
Raman spectroscopy is widely used as a clinical tool in cancer diagnosis. Bone damage and pain caused by cancer cells in the skeleton are serious complications in women suffering from bone metastases associated with advanced breast cancer.
The trickiest part of treating excessive bone loss in women with breast cancer is diagnosing it early enough. In the era of detection kits, we wish to validate the nail keratin test described in our recent studies as a bone metastasis-screening test in mouse models of breast cancer bone metastasis.
And though this remains aspirational, who knows, such a simple, non-invasive detection kit may even be included in routine checks alongside other cancer tests.
Conflict of interest: The study, Raman spectroscopy predicts the link between claw keratin and bone collagen structure in a mouse model of Oestrogen deficiency was recently published in the journal Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease was supported by Crescent Diagnostics Ltd. and Intertrade Ireland (FUSION programme 2012).
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