bromochloroacetic-acid and Osteoporosis

Osteoporosis is a common disease characterised by reduced bone mass and an increased risk of fragility fractures. Low bone mineral density is known to significantly increase the risk of osteoporotic fractures, however, the majority of non-traumatic fractures occur in individuals with a bone mineral density too high to be classified as osteoporotic. Therefore, there is an urgent need to investigate aspects of bone health, other than bone mass, that can predict the risk of fracture. Here, we successfully predicted association between bone collagen and nail keratin in relation to bone loss due to oestrogen deficiency using Raman spectroscopy. Raman signal signature successfully discriminated between ovariectomised rats and their sham controls with a high degree of accuracy for the bone (sensitivity 89%, specificity 91%) and claw tissue (sensitivity 89%, specificity 82%). When tested in an independent set of claw samples the classifier gave 92% sensitivity and 85% specificity. Comparison of the spectral changes occurring in the bone tissue with the changes occurring in the keratin showed a number of common features that could be attributed to common changes in the structure of bone collagen and claw keratin. This study established that systemic oestrogen deficiency mediates parallel structural changes in both the claw (primarily keratin) and bone proteins (primarily collagen). This strengthens the hypothesis that nail keratin can act as a surrogate marker of bone protein status where systemic processes induce changes.

Topics: Animals; Bone and Bones; Bone Density; Collagen; Cytoskeleton; Disease Models, Animal; Estrogens; Female; Hoof and Claw; Keratins; Osteoporosis; Rats; Rats, Sprague-Dawley; Rats, Wistar; Spectrum Analysis, Raman; X-Ray Microtomography

Osteoporosis is a disease with great importance in current public health due to the associated risk of fracture; therefore, a rapid and accurate diagnosis becomes increasingly important. Recent literature has described a possible relationship between the changes in the organic phase of bone and the changes in nail keratin measured through Raman spectroscopy, aiming at the development of a standard for measuring bone quality and fracture risk both rapid and accurately. This work evaluated the correlation between the bone mineral density (BMD) scores of women with and without osteoporotic disease with the changes in the Raman spectra of the nail keratin, by assessing the intensity of the peak at 510 cm(-1) (S-S bridge) and the scores of principal component analysis (PCA), correlated with the values of BMD measured at the lumbar and hip. Raman spectra of ex vivo fingernails of 213 women were obtained by means of a dispersive Raman spectrometer (830 nm, 300 mW, in the spectral range between 400 and 1,800 cm(-1)). Peak intensities at ∼510 cm(-1) (assigned to the keratin S-S bridge) were measured, and the scores of first principal component loading vectors were calculated. Results showed no differences in the mean Raman spectra of nails of groups with and without osteoporosis. No correlation was found between the BMD scores and both the intensities of the 510 cm(-1) peak and the scores of the first four principal component vectors. Results suggest that BMD and fracture risk could not be assessed by the nail keratin features.

Topics: Absorptiometry, Photon; Adult; Aged; Aged, 80 and over; Bone and Bones; Bone Density; Cohort Studies; Densitometry; Female; Humans; Keratins; Middle Aged; Nails; Osteoporosis; Osteoporotic Fractures; Principal Component Analysis; Spectrum Analysis, Raman

Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.

Topics: Bone Density; Collagen; Female; Humans; Keratins; Nails; Osteoporosis; Spectrum Analysis, Raman

Anecdotally, patients volunteer reports of increasing hardness of their fingernails within months of starting diverse treatments for osteoporosis. The properties of both nail and bone may be linked in a comparable, measurable way.. We examined the fingernails of two groups of patients, with (n = 9) and without (n = 13) osteoporosis at either the hip or lumbosacral spine. We performed nanoindentation to assess the degree of nail brittleness and Raman spectroscopy to assess the disulfide bond content of nail.. The mean moduli of fingernails of patients with low bone mineral density (BMD) are lower than those of patients with normal BMD. The mean difference in mean modulus between the groups was found to be 0.996 (p = 0.15 between groups). The spectroscopy data also showed differences between the two sets of nails. The disulfide bond content of the nails sourced from osteoporotic patients was lower than that from healthy patients (p = 0.06 between groups).. Bone collagen and nail keratin are two distinct structural proteins, and both require protein sulfation and disulfide bond formation, via cysteine, for structural integrity. A disorder of either process may lead to disordered collagen and keratin synthesis. This is reflected in the structural abnormalities seen in clinical syndromes in which there is either protein deficiency, disorders of sulfur metabolism, or cystathione beta-synthase deficiency. The relationship between nail and bone may exist in a measurable way. This pilot study should lead to further work to explore this relationship. Could nail prove to be a valuable adjunct to diagnosis or provide a means of more rapid follow-up after commencement of therapy?

Topics: Aged; Bone Density; Case-Control Studies; Collagen; Female; Humans; Keratins; Middle Aged; Nail Diseases; Nails; Osteoporosis; Pilot Projects; Spectrum Analysis, Raman

Three males with the X-linked disorder dyskeratosis congenita are described. Each suffered femoral fractures after minimal trauma with poor healing. Long bones showed coarse trabecular patterns of the metaphyses and small lucency areas in the diaphyses. Two of the males were retarded brothers who additionally showed intracranial calcifications.

Topics: Adolescent; Bone and Bones; Bone Diseases; Calcinosis; Female; Fractures, Bone; Humans; Intellectual Disability; Keratins; Male; Osteoporosis; Radiography; Sex Chromosome Aberrations; Skin Diseases; Skull; Syndrome; X Chromosome

The denture-bearing mucosa of aged maxillary and mandibular ridges show morphologic changes that are irreversible. These changes limit the extensibility and the rebound capacity of the denture-bearing area.

Topics: Adolescent; Aged; Aging; Alveolar Process; Arteriosclerosis; Collagen; Connective Tissue; Female; Humans; Keratins; Male; Mouth Mucosa; Mouth, Edentulous; Osteoporosis