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Absorption and Bioavailability of Nano-Size Reduced Calcium Citrate Fortified Milk Powder in Ovariectomized and Ovariectomized-Osteoporosis Rats

Erfanian A, Mirhosseini H, Rasti B, Hair-Bejo M, Bin Mustafa S, Abd Manap MY

J Agric Food Chem, 2015 Jun 24;63(24):5795-804.
PMID: 26022498 DOI: 10.1021/acs.jafc.5b01468

The aim of this study was to evaluate the effects of fortification and nano-size reduction on calcium absorption and bioavailability of milk powder formula in sham, ovariectomized, and ovariectomized-osteoporosis rats as a menopause and menopause-osteoporosis model. Skim milk powder and skim milk powder fortified with calcium citrate and the suitable doses of inulin, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamins D3, K1, and B6 were formulated based on the North American and Western European recommended dietary allowances. Optimization on cycle and pressure of high-pressure homogenizer was done to produce nano-fortified milk powder. In vivo study demonstrated that fortification and calcium citrate nano-fortified milk powder increased absorption and bioavailability of calcium, as well as bone stiffness and bone strength in sham, ovariectomized, and ovariectomized-osteoporosis rats. This study successfully developed an effective fortified milk powder for food application.

Matched MeSH terms: Osteoporosis/drug therapy*
Pregnancy-associated osteoporosis: a UK case series and literature review

Hardcastle SA, Yahya F, Bhalla AK

Osteoporos Int, 2019 May;30(5):939-948.
PMID: 30671611 DOI: 10.1007/s00198-019-04842-w

Mini Abstract: Pregnancy-associated osteoporosis (PAO) is a rare syndrome affecting women during late pregnancy and the early postpartum period. We set out to review the clinical features of ten cases of PAO from a single UK centre. Patients had attended the Royal National Hospital for Rheumatic Diseases, Bath (RNHRD) between January 2000 and June 2016. The principal criterion for inclusion was the occurrence of low trauma fractures either during pregnancy or the immediate post-partum period. Data were obtained from retrospective review of medical notes. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (Hologic ®Discovery system) at the lumbar spine and hip. Data pertaining to the pregnancy, as well as type and duration of treatment received, were reviewed. All ten cases presented with vertebral fractures. In four patients, no risk factors for fracture other than pregnancy or breastfeeding could be identified. Four patients were found to have vitamin D insufficiency at the time of diagnosis, and a further two patients had received treatment with low molecular weight heparin (LMWH). In one case, further investigation led to a diagnosis of osteogenesis imperfecta (OI) confirmed on genetic testing. In terms of treatment, eight out of the ten patients in this series received a bisphosphonate, most commonly risedronate due to its relatively short skeletal retention time. Clinicians should be aware of PAO, a rare but recognised complication of pregnancy. The condition should be especially considered in women presenting with new onset back pain in pregnancy or the postpartum period.

Matched MeSH terms: Osteoporosis/drug therapy
Bisphosphonates, healthcare professionals and oral health

Raj DV, Abuzar M, Borromeo GL

Gerodontology, 2016 Mar;33(1):135-43.
PMID: 25039439 DOI: 10.1111/ger.12141

OBJECTIVE: General medical and dental practitioner and pharmacists all encounter patients on bisphosphonates and as such require adequate knowledge regarding osteonecrosis of the jaw, a potential complication associated with its use. The cross-sectional study investigated perceived implications of and attitudes towards bisphosphonate use in oral health among general medical and dental practitioners and pharmacists.
MATERIALS AND METHODS: Medical and dental practitioners and pharmacists registered in Victoria, Australia, completed an online survey (SurveyMonkey©). Data analysis consisted of chi-square tests with significance as p < 0.05.
RESULTS: One hundred and thirty six doctors (general medical practitioners, GMPs), 283 dentists (GDPs) and 26 pharmacists (PHs) participated. 70, 38 and 80%, respectively, reviewed patients prescribed bisphosphonates (BPs). GMPs (88%), GDPs (76%) and PHs (85%) were aware of osteonecrosis of the jaws (ONJ). GMPs (76%) and PHs (100%) advised patients to inform dentists. GMPs (45%) referred patients for dental assessments prior to commencing BPs with 71.9% of GDPs received such referrals. In terms of available information on oral health and BPs, GMPs (56%), GDPs (50%) and PH (53.8%) were either unsure any existed or reported receiving sufficient information.
CONCLUSIONS: Discrepancies exist amongst different healthcare professionals in terms of BP use and oral health, and common consensus guidelines are warranted.
KEYWORDS: bisphosphonates; clinical guidelines; drug therapy; oral health; osteonecrosis.

Matched MeSH terms: Osteoporosis/drug therapy
Fulltext Are Oxidative Stress and Inflammation Mediators of Bone Loss Due to Estrogen Deficiency? A Review of Current Evidence

Mohamad NV, Ima-Nirwana S, Chin KY

Endocr Metab Immune Disord Drug Targets, 2020;20(9):1478-1487.
PMID: 32496996 DOI: 10.2174/1871530320666200604160614

Osteoporosis is one of the major health issues associated with menopause-related estrogen deficiency. Various reports suggest that the hormonal changes related to menopausal transition may lead to the derangement of redox homeostasis and ultimately oxidative stress. Estrogen deficiency and oxidative stress may enhance the expression of genes involved in inflammation. All these factors may contribute, in synergy, to the development of postmenopausal osteoporosis. Previous studies suggest that estrogen may act as an antioxidant to protect the bone against oxidative stress, and as an antiinflammatory agent in suppressing pro-inflammatory and pro-osteoclastic cytokines. Thus, the focus of the current review is to examine the relationship between estrogen deficiency, oxidative stress and inflammation, and the impacts of these phenomena on skeletal health in postmenopausal women.

Matched MeSH terms: Osteoporosis/drug therapy
Effects of tocotrienol from Bixa orellana (annatto) on bone histomorphometry in a male osteoporosis model induced by buserelin

Mohamad NV, Soelaiman IN, Chin KY

Biomed Pharmacother, 2018 Jul;103:453-462.
PMID: 29674281 DOI: 10.1016/j.biopha.2018.04.083

INTRODUCTION: Osteoporosis is a debilitating skeletal side effect of androgen deprivation therapy based on gonadotropin-releasing hormone (GnRH) agonist in men. Tocotrienol from Bixa orellana (annatto) has been demonstrated to offer protection against osteoporosis by exerting anabolic effects on bone. Thus, it may prevent osteoporosis among GnRH agonist users.
OBJECTIVE: This study aimed to determine the effectiveness of annatto-tocotrienol on the bone turnover markers and bone histomorphometry in a model of male osteoporosis induced by buserelin (a GnRH agonist).
METHODS: Forty-six three-months-old male Sprague-Dawley rats (three months old; 300-350 g) were randomly divided into six groups. The baseline control group (n = 6) was sacrificed at the onset of the study. The normal control group (n = 8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n = 8) received corn oil orally daily and subcutaneous buserelin injection 75 μg/kg/day daily. The calcium control (n = 8) received 1% calcium in drinking water and subcutaneous buserelin injection 75 μg/kg/day. The remaining rats were treated with two different treatments, i.e., (1) oral annatto tocotrienol at 60 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8); (2) oral annatto tocotrienol at 100 mg/kg/day plus subcutaneous buserelin injection 75 μg/kg/day (n = 8). The rats were injected with calcein twice before being sacrificed to label the bones. The rats were euthanized, and their blood and right femur were harvested at the end of the treatment for bone turnover markers and bone histomorphometry examination.
RESULTS: Both serum osteocalcin and C-telopeptide of type 1 collagen were not significantly different between treated groups and buserelin control (P > 0.05). The buserelin control group had a significantly lower bone volume and higher eroded surface compared with the normal control group (P 

Matched MeSH terms: Osteoporosis/drug therapy*
Fulltext Effect of tocotrienol from Bixa orellana (annatto) on bone microstructure, calcium content, and biomechanical strength in a model of male osteoporosis induced by buserelin

Mohamad NV, Ima-Nirwana S, Chin KY

Drug Des Devel Ther, 2018;12:555-564.
PMID: 29588572 DOI: 10.2147/DDDT.S158410

Background: Patients receiving androgen deprivation therapy experience secondary hypogonadism, associated bone loss, and increased fracture risk. It has been shown that tocotrienol from Bixa orellana (annatto) prevents skeletal microstructural changes in rats experiencing primary hypogonadism. However, its potential in preventing bone loss due to androgen deprivation therapy has not been tested. This study aimed to evaluate the skeletal protective effects of annatto tocotrienol using a buserelin-induced osteoporotic rat model.
Methods: Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.
Results: Annatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.
Conclusion: Annatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.

Matched MeSH terms: Osteoporosis/drug therapy
Fulltext Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist

Mohamad NV, Che Zulkepli MAA, May Theseira K, Zulkifli N, Shahrom NQ, Ridzuan NAM, et al.

Int J Med Sci, 2018;15(4):300-308.
PMID: 29511366 DOI: 10.7150/ijms.22732

Introduction: Orchidectomy is currently the preferred method to induce bone loss in preclinical male osteoporosis model. Gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer treatment can induce testosterone deficiency but its effects on bone in preclinical male osteoporosis model are less studied. Objective: This study aimed to evaluate the skeletal effect of buserelin (a GnRH agonist) in male rats and compare it with orchidectomy. Methods: Forty-six three-month-old male Sprague-Dawley rats were divided into three experimental arms. The baseline arm (n=6) was sacrificed at the onset of the study. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline (n=8), buserelin acetate at 25 µg/kg (n=8) or 75 µg/kg (n=8). In the orchidectomy arm, the rats were either sham-operated (n=8) or orchidectomized (n=8). All groups underwent in-vivo X-ray micro-computed tomography scanning at the left proximal tibia every month. Blood was collected at the beginning and the end of the study for testosterone level evaluation. The rats were euthanized after the three-month treatment. The femurs were harvested for biomechanical strength and bone calcium determination. Results: The results showed that buserelin at both doses caused a significant decline in testosterone level and deterioration in bone microstructure (p<0.05), but did not affect bone calcium content (p>0.05). Buserelin at 25 µg/kg decreased displacement and strain of the femur significantly (p<0.05). Similar changes were observed in the orchidectomized group compared to the sham-operated group but without any significant changes in biomechanical strength (p>0.05). Conclusion: Buserelin can induce testosterone deficiency and the associated deterioration of bone microarchitecture similar to orchidectomy in three months. However, it may require a longer time to show significant effects on bone strength and mineral content.

Matched MeSH terms: Osteoporosis/drug therapy*
Editorial: novel agents in the treatment of osteoporosis and its complications

Shuid AN, Soelaiman IN, Das S

Curr Drug Targets, 2013 Dec;14(13):1523.
PMID: 24266612
Matched MeSH terms: Osteoporosis/drug therapy*
Novel agents in the treatment of osteoporosis

Shuid AN, Ima Nirwana S, Das S

Curr Drug Targets, 2013 Dec;14(14):1631.
PMID: 24383964
Matched MeSH terms: Osteoporosis/drug therapy*
Management of corticosteroid-induced osteoporosis

Yeap SS, Hosking DJ

Rheumatology (Oxford), 2002 Oct;41(10):1088-94.
PMID: 12364625 DOI: 10.1093/rheumatology/41.10.1088

Corticosteroid (CS) therapy is widely used in the treatment of rheumatic diseases. Osteoporosis remains one of its major complications. The risk of low bone mineral density (BMD) and fracture may be already increased in some of the rheumatic diseases, regardless of CS therapy. However, in spite of this, preventative treatment for osteoporosis in patients on CS remains low. Patients on or about to start CS use for more than 6 months are at risk of corticosteroid-induced osteoporosis (CIOP). The pathogenesis of CIOP differs from post-menopausal osteoporosis in that bone formation is said to be more suppressed compared with bone resorption. The diagnosis of CIOP can be made on clinical risk factors and may not require measurement of BMD. Many agents used in post-menopausal osteoporosis such as activated vitamin D products, hormone replacement therapy, fluoride, calcitonin and the bisphosphonates have been shown to maintain or improve BMD in CIOP. However, there are few data on the reduction in fracture rates in CIOP, but the bisphosphonates seem the most promising in this regard.

Matched MeSH terms: Osteoporosis/drug therapy*
Regulatory actions of 3',5'-cyclic adenosine monophosphate on osteoclast function: possible roles of Epac-mediated signaling

Jeevaratnam K, Salvage SC, Li M, Huang CL

Ann N Y Acad Sci, 2018 Dec;1433(1):18-28.
PMID: 29846007 DOI: 10.1111/nyas.13861

Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.

Matched MeSH terms: Osteoporosis/drug therapy
Synergistic effects of combined therapy of curcumin and Fructus Ligustri Lucidi for treatment of osteoporosis: cellular and molecular evidence of enhanced bone formation

Bukhari SNA, Hussain F, Thu HE, Hussain Z

J Integr Med, 2019 Jan;17(1):38-45.
PMID: 30139656 DOI: 10.1016/j.joim.2018.08.003

OBJECTIVE: The present study explored the effects of the combined herbal therapy consisting of curcumin (CUR) and Fructus Ligustri Lucidi (FLL) on aspects of bone regeneration.
METHODS: Prior to analyzing the ability of this novel combined herbal therapy to promote aspects of bone regeneration, its cytotoxicity was determined using MC3T3-E1 cells (pre-osteoblast model). Cell proliferation was evaluated using phase-contrast microscopy and cell differentiation was estimated using alkaline phosphatase activity. The effect of the combined herbal therapy (CUR + FLL) was also assessed in terms of mineralization in the extracellular matrix (ECM) of cultured cells. Further, to explore the molecular mechanisms of bone formation, time-dependent expression of bone-regulating protein biomarkers was also evaluated.
RESULTS: Combined herbal therapy (CUR + FLL) significantly upregulated the viability, proliferation and differentiation of MC3T3-E1 cells compared to the monotherapy of CUR or FLL. The magnitude of ECM mineralization (calcium deposition) was also higher in MC3T3-E1 cells treated with combined therapy. The time-dependent expression of bone-forming protein biomarkers revealed that the tendency of expression of these bone-regulating proteins was remarkably higher in cells treated with combined therapy.
CONCLUSION: The co-administration of CUR and FLL had superior promotion of elements of bone regeneration in cultured cells, thus could be a promising alternative herbal therapy for the management of bone erosive disorders such as osteoporosis.

Matched MeSH terms: Osteoporosis/drug therapy*
Fulltext Comparison of diclofenac with apigenin-glycosides rich Clinacanthus nutans extract for amending inflammation and catabolic protease regulations in osteoporotic-osteoarthritis rat model

Tantowi NACA, Mohamed S, Lau SF, Hussin P

Daru, 2020 Dec;28(2):443-453.
PMID: 32388789 DOI: 10.1007/s40199-020-00343-y

BACKGROUND: Osteoporotic-osteoarthritis is an incapacitating musculoskeletal illness of the aged.
OBJECTIVES: The anti-inflammatory and anti-catabolic actions of Diclofenac were compared with apigenin-C-glycosides rich Clinacanthus nutans (CN) leaf extract in osteoporotic-osteoarthritis rats.
METHODS: Female Sprague Dawley rats were randomized into five groups (n = 6). Four groups were bilateral ovariectomised for osteoporosis development, and osteoarthritis were induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joints. The Sham group was sham-operated, received saline injection and deionized drinking water. The treatment groups were orally given 200 or 400 mg extract/kg body weight or 5 mg diclofenac /kg body weight daily for 28 days. Articular cartilage and bone changes were monitored by gross and histological structures, micro-CT analysis, serum protein biomarkers, and mRNA expressions for inflammation and catabolic protease genes.
RESULTS: HPLC analysis confirmed that apigenin-C-glycosides (shaftoside, vitexin, and isovitexin) were the major compounds in the extract. The extract significantly and dose-dependently reduced cartilage erosion, bone loss, cartilage catabolic changes, serum osteoporotic-osteoarthritis biomarkers (procollagen-type-II-N-terminal-propeptide PIINP; procollagen-type-I-N-terminal-propeptide PINP; osteocalcin), inflammation (IL-1β) and mRNA expressions for nuclear-factor-kappa-beta NF-κβ, interleukin-1-beta IL-1β, cyclooxygenase-2; and matrix-metalloproteinase-13 MMP13 activities, in osteoporotic-osteoarthritis rats comparable to Diclofenac.
CONCLUSION: This study demonstrates that apigenin-C-glycosides at 400 mg CN extract/kg (about 0.2 mg apigenin-equivalent/kg) is comparable to diclofenac in suppressing inflammation and catabolic proteases for osteoporotic-osteoarthritis prevention. Graphical abstract.

Matched MeSH terms: Osteoporosis/drug therapy*
Fulltext Annatto tocotrienol improves indices of bone static histomorphometry in osteoporosis due to testosterone deficiency in rats

Chin KY, Abdul-Majeed S, Fozi NF, Ima-Nirwana S

Nutrients, 2014 Nov;6(11):4974-83.
PMID: 25389899 DOI: 10.3390/nu6114974

This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05). The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent.

Matched MeSH terms: Osteoporosis/drug therapy*
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: Osteoporosis/drug therapy
Fulltext Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats

Chin KY, Ima-Nirwana S

Clin Interv Aging, 2014;9:1247-59.
PMID: 25120355 DOI: 10.2147/CIA.S67016

BACKGROUND: Previous animal models have demonstrated that tocotrienol is a potential treatment for postmenopausal osteoporosis. This study evaluated the antiosteoporotic effects of annatto-derived tocotrienol (AnTT) using a testosterone-deficient osteoporotic rat model.
METHODS: Forty rats were divided randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The baseline group was euthanized without undergoing any surgical treatment or intervention. The remaining groups underwent orchidectomy, with the exception of the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the testosterone group received testosterone enanthate 7 mg/kg per week intramuscularly for 8 weeks. Structural changes in trabecular bone at the proximal tibia were examined using microcomputed tomography. Structural and dynamic changes at the distal femur were examined using histomorphometric methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were measured. Bone-related gene expression in the distal femur was examined.
RESULTS: There were significant degenerative changes in structural indices in the orchidectomized group (P<0.05), but no significant changes in dynamic indices, bone remodeling markers, or gene expression (P>0.05) when compared with the sham group. The AnTT group showed significant improvement in structural indices at the femur (P<0.05) and significantly increased expression of bone formation genes (P<0.05). Testosterone was more effective than AnTT in preventing degeneration of bone structural indices in the femur and tibia (P<0.05).
CONCLUSION: AnTT supplementation improves bone health in testosterone-deficient rats by enhancing bone formation. Its potential should be evaluated further by varying the dosage and treatment duration.
KEYWORDS: bone remodeling; osteoporosis; testosterone; tocotrienol

Matched MeSH terms: Osteoporosis/drug therapy*
Fulltext The effects of α-tocopherol on bone: a double-edged sword?

Chin KY, Ima-Nirwana S

Nutrients, 2014 Apr;6(4):1424-41.
PMID: 24727433 DOI: 10.3390/nu6041424

Recent studies have found conflicting evidence on the role of α-tocopherol (αTF) on bone health. This nonsystematic review aimed to summarize the current evidence on the effects of αTF on bone health from cell culture, animal, and human studies in order to clarify the role of αTF on bone health. Our review found that αTF exerted beneficial, harmful or null effects on bone formation cells. Animal studies generally showed positive effects of αTF supplementation on bone in various models of osteoporosis. However, high-dose αTF was possibly detrimental to bone in normal animals. Human studies mostly demonstrated a positive relationship between αTF, as assessed using high performance liquid chromatography and/or dietary questionnaire, and bone health, as assessed using bone mineral density and/or fracture incidence. Three possible reasons high dosage of αTF can be detrimental to bone include its interference with Vitamin K function on bone, the blocking of the entry of other Vitamin E isomers beneficial to bone, and the role of αTF as a prooxidant. However, these adverse effects have not been shown in human studies. In conclusion, αTF may have a dual role in bone health, whereby in the appropriate doses it is beneficial but in high doses it may be harmful to bone.

Matched MeSH terms: Osteoporosis/drug therapy
Piper sarmentosum: a new hope for the treatment of osteoporosis

Mohd Ramli ES, Suhaimi F, Ahmad F, Shuid AN, Mohamad N, Ima-Nirwana S

Curr Drug Targets, 2013 Dec;14(14):1675-82.
PMID: 24107234

Osteoporosis is a major global health problem. Osteoporosis is characterized by the loss of bone mass and strength which leads to an increased risk of fracture. Glucocorticoid treatment is the leading cause of secondary osteoporosis. Glucocorticoid action in bone depends upon the expression of 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). The oestrogen deficient state causes osteoporosis due to enhancement of osteoclastogenesis by oxidative stress which leads to increased bone resorption. Piper sarmentosum (Daun Kaduk) is commonly used in the local cuisine of South East Asia. It is also traditionally used to treat many diseases such as inflammation, dermatitis and joint pain. Studies have revealed antioxidant properties through its flavonoids compound naringenin which acts as a superoxide scavenger that may help in the endogenous antioxidant defence system to protect bone against osteoporosis. Recent studies found that Ps extract has the ability to inhibit the expression and activity of 11β-HSD1 in adipose tissue and bone which restored bone structure and strength. It also accelerates fracture healing in the oestrogen deficient state through its antioxidant properties. The cost of conventional treatment is high and together with the adverse effects it leads to noncompliance. Treatment modalities with herbal medicine, less side effects and is cheaper need to be explored.This review focused on the therapeutic effect of Ps extract on fracture healing in ovariectomized rats and its protective effects against glucocorticoid induced osteoporotic rats.

Matched MeSH terms: Osteoporosis/drug therapy*
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: Osteoporosis/drug therapy*
Berberine and musculoskeletal disorders: The therapeutic potential and underlying molecular mechanisms

Wong SK, Chin KY, Ima-Nirwana S

Phytomedicine, 2020 Jul 15;73:152892.
PMID: 30902523 DOI: 10.1016/j.phymed.2019.152892

BACKGROUND: Musculoskeletal disorders are a group of disorders that affect the joints, bones, and muscles, causing long-term disability. Berberine, an isoquinoline alkaloid, has been previously established to exhibit beneficial properties in preventing various diseases, including musculoskeletal disorders.
PURPOSE: This review article aims to recapitulate the therapeutic potential of berberine and its mechanism of action in treating musculoskeletal disorders.
METHODS: A wide range of literature illustrating the effects of berberine in ameliorating musculoskeletal disorders was retrieved from online electronic databases (PubMed and Medline) and reviewed.
RESULTS: Berberine may potentially retard the progression of osteoporosis, osteoarthritis and rheumatoid arthritis. Limited studies reported the effects of berberine in suppressing the proliferation of osteosarcoma cells. These beneficial properties of berberine are mediated in part through its ability to target multiple signaling pathways, including PKA, p38 MAPK, Wnt/β-catenin, AMPK, RANK/RANKL/OPG, PI3K/Akt, NFAT, NF-κB, Hedgehog, and oxidative stress signaling. In addition, berberine exhibited anti-apoptotic, anti-inflammatory, and immunosuppressive properties.
CONCLUSION: The current evidence indicates that berberine may be effective in preventing musculoskeletal disorders. However, findings from in vitro and in vivo investigations await further validation from human clinical trial.

Matched MeSH terms: Osteoporosis/drug therapy

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