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The effects of orchidectomy and supraphysiological testosterone administration on trabecular bone structure and gene expression in rats

Chin KY, Ima-Nirwana S

Aging Male, 2015 Mar;18(1):60-6.
PMID: 25166624 DOI: 10.3109/13685538.2014.954995

This study aimed to determine the effects of orchidectomy and supraphysiological testosterone replacement on trabecular structure and gene expression in the bone.

Matched MeSH terms: Tibia/drug effects
Effects of non-antibiotic feed additives on performance, tibial dyschondroplasia incidence and tibia characteristics of broilers fed low-calcium diets

Houshmand M, Azhar K, Zulkifli I, Bejo MH, Meimandipour A, Kamyab A

J Anim Physiol Anim Nutr (Berl), 2011 Jun;95(3):351-8.
PMID: 21156001 DOI: 10.1111/j.1439-0396.2010.01061.x

This experiment was conducted to investigate and compare the efficacy of different feed additives on performance, tibial dyschondroplasia (TD) incidence and tibia characteristics of male broilers fed low-calcium diets. A completely randomized design, with six treatments and five replicates of five chicks per each was used. Experimental treatments were: (i) Basal diet containing recommended level of calcium (0.9%) as control treatment (Ctrl), (ii) low-calcium (0.67%) diet without any additive (LC), (iii) low-calcium diet + probiotic (2 g/kg diet), (iv) low-calcium diet + prebiotic (2 g/kg diet), (v) low-calcium diet + synbiotic [mix of probiotic and prebiotic (each 2 g/kg diet)], (vi) low-calcium diet + organic acid (1.5 g/kg diet). Birds were reared in an open-sided house system under natural tropical condition until 21 days of age. Feeding with low-calcium diet negatively influenced broiler performance (body weight, body weight gain and feed conversion ratio) and tibia characteristics, whereas dietary inclusion of all feed additives had beneficial effects on above-mentioned parameters and helped the birds to overcome problems related to low-calcium diets. Different treatments had no effect on TD incidence.

Matched MeSH terms: Tibia/drug effects
Ceftaroline fosamil laden allograft: A new modality in reducing infection?

Singh VA, Sim LH, Haseeb A, Ju CTS

J Orthop Surg (Hong Kong), 2018 10 23;26(3):2309499018806671.
PMID: 30343651 DOI: 10.1177/2309499018806671

PURPOSE: Allograft infection remains the greatest challenge in orthopaedic reconstructive surgery especially methicillin-resistant Staphylococcus aureus (MRSA). This risk can be minimized with the use of antibiotic laden allograft (ALA) via iontophoresis. Ceftaroline fosamil (CF) is an advanced-generation cephalosporin, an alternative treatment for MRSA infections. Its antibacterial activity and safety profile are better than vancomycin. CF iontophoresed bone has not been used before. This study was conducted to establish the feasibility of creating a CF ALA and establish the prime conditions for its expenditure.
METHOD: We created an iontophoresis cell; 3% CF was inserted within medullary segment of goat bone and sealed from external saline solution. The cell operated at the following voltages 30, 60 and 90 V and at the following durations 5, 10, 15, 20, 25 and 30 min. Information regarding optimal conditions for its application was then obtained. After which, correlation between voltages and time with CF concentration in the bone was analysed. A bioavailability test was also conducted to observe the optimal rate of CF elution from the graft.
RESULT: The optimal condition for the impregnation process is 3% CF at 90 V for 10 min. Bone graft impregnated with CF at optimal conditions can elute above minimum inhibitory concentration of the CF against MRSA for 21 days.
CONCLUSION: CF iontophoresis was found feasible for allograft impregnation. The technique is simple, inexpensive and reproducible clinically. Iontophoresis offers a novel solution to reduce the rate of perioperative infection in reconstructive surgery involving use of bone graft.

Matched MeSH terms: Tibia/drug effects
Fulltext The Effects of Tocotrienol on Bone Peptides in a Rat Model of Osteoporosis Induced by Metabolic Syndrome: The Possible Communication between Bone Cells

Wong SK, Chin KY, Ima-Nirwana S

Int J Environ Res Public Health, 2019 09 09;16(18).
PMID: 31505801 DOI: 10.3390/ijerph16183313

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.

Matched MeSH terms: Tibia/drug effects*
Stable Incretin Mimetics Counter Rapid Deterioration of Bone Quality in Type 1 Diabetes Mellitus

Mansur SA, Mieczkowska A, Bouvard B, Flatt PR, Chappard D, Irwin N, et al.

J Cell Physiol, 2015 Dec;230(12):3009-18.
PMID: 26016732 DOI: 10.1002/jcp.25033

Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidences suggest a beneficial effect of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of bone strength at the organ and tissue level; and to ascertain whether enzyme resistant GIP or GLP-1 mimetic could be beneficial in preventing bone fragility in type 1 diabetes mellitus. Streptozotocin-treated mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-diabetic animals were treated for 21 days with an enzymatic-resistant GIP peptide ([D-Ala(2) ]GIP) or with liraglutide (each at 25 nmol/kg bw, ip). Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation, and Fourier-transform infrared microspectroscopy. [D-Ala2]GIP and liraglutide treatment did prevent loss of whole bone strength and cortical microstructure in the STZ-injected mice. However, tissue material properties were significantly improved in STZ-injected animals following treatment with [D-Ala2]GIP or liraglutide. Treatment of STZ-diabetic mice with [D-Ala(2) ]GIP or liraglutide was capable of significantly preventing deterioration of the quality of the bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to human patients.

Matched MeSH terms: Tibia/drug effects*
The Effects of Annatto Tocotrienol on Bone Biomechanical Strength and Bone Calcium Content in an Animal Model of Osteoporosis Due to Testosterone Deficiency

Chin KY, Gengatharan D, Mohd Nasru FS, Khairussam RA, Ern SL, Aminuddin SA, et al.

Nutrients, 2016 Dec 14;8(12).
PMID: 27983628

Osteoporosis reduces the skeletal strength and increases the risk for fracture. It is an underdiagnosed disease in men. Annatto tocotrienol has been shown to improve bone structural indices and increase expression of bone formation genes in orchidectomized rats. This study aimed to evaluate the effects of annatto tocotrienol on biomechanical strength and calcium content of the bone in orchidectomized rats. Thirty three-month-old male Sprague-Dawley rats were randomly assigned to five groups. The baseline control (BC) group was sacrificed at the onset of the study. The sham-operated group (SHAM) received olive oil (the vehicle of tocotrienol) orally daily and peanut oil (the vehicle of testosterone) intramuscularly weekly. The remaining rats were orchidectomized and treated with three different regimens, i.e., (1) daily oral olive oil plus weekly intramuscular peanut oil injection; (2) daily oral annatto tocotrienol at 60 mg/kg plus weekly intramuscular peanut oil injection; (3) daily oral olive oil plus weekly intramuscular testosterone enanthate injection at 7 mg/kg. Blood, femur and tibia of the rats were harvested at the end of the two-month treatment period for the evaluation of serum total calcium and inorganic phosphate levels, bone biomechanical strength test and bone calcium content. Annatto-tocotrienol treatment improved serum calcium level and tibial calcium content (p < 0.05) but it did not affect femoral biomechanical strength (p > 0.05). In conclusion, annatto-tocotrienol at 60 mg/kg augments bone calcium level by preventing calcium mobilization into the circulation. A longer treatment period is needed for annatto tocotrienol to exert its effects on bone strength.

Matched MeSH terms: Tibia/drug effects