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The Role of Dietary Compounds in the Therapy of Nicotine-Induced Osteoporosis

Mohamed N, Muhammad N, Shuid AN, Soelaiman IN

Curr Drug Targets, 2018;19(12):1424-1430.
PMID: 28950810 DOI: 10.2174/1389450118666170925154428

Nicotine is one of the most abused substances worldwide and can cause several harmful effects on health. One of the harmful effects, which is often ignored, is osteoporosis. Smoking has been shown to cause a decrease in bone mineral density in humans. Animal studies have proven that nicotine exerts negative effects on bone. The number of people who smoke increases each day. Those who smoke start at a very young age and they usually smoke for years. This will increase the risk of developing osteoporosis. As the prevalence of osteoporosis increases, the risk of fractures also increases. The major concerns are disability following fractures, mortality due to complications after fractures and the increasing cost of management and therapy. This paper will review the effects of nicotine on bone and the potential natural products which can be used as treatment for nicotine-induced osteoporosis.

Matched MeSH terms: Osteoporosis/chemically induced*
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/chemically induced*
Influences on bone mineral density in Malaysian premenopausal systemic lupus erythematosus patients on corticosteroids

Yeap SS, Fauzi AR, Kong NC, Halim AG, Soehardy Z, Rahimah S, et al.

Lupus, 2009 Feb;18(2):178-81.
PMID: 19151123 DOI: 10.1177/0961203308094995

The aim of this study was to assess the bone mineral density (BMD) of premenopausal patients with systemic lupus erythematosus (SLE) on corticosteroids (CS) and to determine the influence of CS and other risk factors on BMD. A total of 98 premenopausal patients with SLE were recruited from outpatient clinics in two teaching hospitals. Risk factors for osteoporosis were determined, and BMD was measured using dual-energy x-ray absorptiometry. The mean age of the patients was 30.05 +/- 7.54 years. The mean dose of prednisolone at time of BMD measurement was 18.38 +/- 10.85 mg daily. Median duration of CS use was 2.5 years (range 0-20). Median cumulative dose of CS was 9.04 g (range 0.28-890.0). Six patients (6.1%) had osteoporosis, 41 (41.9%) had osteopenia and 51 (52.0%) had normal BMD. Lumbar spine T score correlated with cumulative CS dose (P = 0.019). Duration of CS intake correlated with femoral neck T score (P = 0.04) and trochanter T score (P = 0.008). There was no correlation between BMD and race, SLE Disease Activity Index score, smoking and self-reported calcium intake or exercise. Only 52% of these patients had normal BMD. The duration and cumulative dose of CS intake was significantly correlated to BMD, but not the other commonly assessed risk factors. These findings suggest that premenopausal patients with SLE on CS should have their BMD measured at regular intervals to fully assess their osteoporosis risk.

Study site: outpatient clinics in two teaching hospitals

Matched MeSH terms: Osteoporosis/chemically induced*
Fulltext Corticosteroids causing severe growth suppression in juvenile rheumatoid arthritis

Lyn PCW

Med J Malaysia, 1984 Dec;39(4):300-5.
PMID: 6544938

Two children with Juvenile Rheumatoid Arthritis (JRA) and severe growth suppression from corticosteroid therapy are described. Prolonged 'tailing-off' of steroids occurred during outpatients follow-up and this may be related to the high turnover of doctors involved. Suggestions for improving such follow-ups and caution against the continuous use of steroids are made.
Study site: Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

Matched MeSH terms: Osteoporosis/chemically induced
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/chemically induced
Beneficial effects of tocotrienol and tocopherol on bone histomorphometric parameters in sprague-dawley male rats after nicotine cessation

Hermizi H, Faizah O, Ima-Nirwana S, Ahmad Nazrun S, Norazlina M

Calcif. Tissue Int., 2009 Jan;84(1):65-74.
PMID: 19020790 DOI: 10.1007/s00223-008-9190-x

This study was conducted to determine the effectiveness of three forms of vitamin E supplements following nicotine treatment on bone histomorphometric parameters in an adult male rat model. Rats were divided into seven groups: baseline (B, killed without treatment), control (C, normal saline for 4 months), nicotine (N, nicotine for 2 months), nicotine cessation (NC), tocotrienol-enhanced fraction (TEF), gamma-tocotrienol (GTT), and alpha-tocopherol (ATF). Treatments for the NC, TEF, GTT, and ATF groups were performed in two phases. For the first 2 months they were given nicotine (7 mg/kg), and for the following 2 months nicotine administration was stopped and treatments with respective vitamin E preparations (60 mg/kg) were commenced except for the NC group, which was allowed to recover without treatment. Rats in the N and NC groups had lower trabecular bone volume, mineral appositional rate (MAR), and bone formation rate (BFR/BS) and higher single labeled surface and osteoclast surface compared to the C group. Vitamin E treatment reversed these nicotine effects. Both the TEF and GTT groups, but not the ATF group, had a significantly higher trabecular thickness but lower eroded surface (ES/BS) than the C group. The tocotrienol-treated groups had lower ES/BS than the ATF group. The GTT group showed a significantly higher MAR and BFR/BS than the TEF and ATF groups. In conclusion, nicotine induced significant bone loss, while vitamin E supplements not only reversed the effects but also stimulated bone formation significantly above baseline values. Tocotrienol was shown to be slightly superior compared to tocopherol. Thus, vitamin E, especially GTT, may have therapeutic potential to repair bone damage caused by chronic smoking.

Matched MeSH terms: Osteoporosis/chemically induced
Fulltext Steroid-induced osteoporosis--a cause for concern?

Tan TT, Lau IS, Kong NC, Zainal AG

Malays J Pathol, 1997 Jun;19(1):27-33.
PMID: 10879239
Matched MeSH terms: Osteoporosis/chemically induced*
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/chemically induced
Fulltext Damage in the multiethnic Malaysian systemic lupus erythematosus (SLE) cohort: Comparison with other cohorts worldwide

Shaharir SS, Hussein H, Rajalingham S, Mohamed Said MS, Abdul Gafor AH, Mohd R, et al.

PLoS One, 2016;11(11):e0166270.
PMID: 27846298 DOI: 10.1371/journal.pone.0166270

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease and despite the improvement in the survival in the past few decades, the morbidity due to disease damage remains significant. The objectives of this study were to investigate the disease damagepattern and determine the associated factors of damage in the multi-ethnic Malaysian SLE patients. We consecutively 424SLE patients who attended a consistent follow-up at the National University of Malaysia Medical Centre and Putrajaya Hospital were recruited. Disease damage was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index (SDI) scores. Information on their demographics and disease characteristics were obtained from the clinical record. Univariate analysis was performed and the best model of independent predictors of disease damage was determined by multivariate logistic regression analysis. A total of 182 patients (42.9%) had disease damage (SDI ≥1). A significantly higher number of Indian patients had disease/organ damage and they predominantly developed steroid-induced diabetes mellitus (SDM). Patients with corticosteroid-induced osteoporosis (CIOP) were more likely to be Malayswhile majority of patients who developed malignancy were Chinese (p<0.05). In the univariate and multivariate analyses, disease damage was significantly associated with age, Indian ethnicity, lower mean cumulative C3 level, neuropsychiatry lupus (NPSLE), and antiphospholipid syndrome (APLS). Patients who had ever and early treatment with hydroxychloroquine(HCQ)were less likely to develop disease damage while more patients who had received oral prednisolone ≥1mg/kg daily over 2 weeks had disease damage (p<0.05). In conclusion, there were inter-ethnic differences in the damage pattern and risks among SLE patients.

Matched MeSH terms: Osteoporosis/chemically induced
Bone loss with antiepileptic drug therapy: a twin and sibling study

Shiek Ahmad B, Petty SJ, Gorelik A, O'Brien TJ, Hill KD, Christie JJ, et al.

Osteoporos Int, 2017 Sep;28(9):2591-2600.
PMID: 28589417 DOI: 10.1007/s00198-017-4098-9

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility.
INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use.
METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated.
RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031).
CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Matched MeSH terms: Osteoporosis/chemically induced*
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/chemically induced
A comparison of calcium, calcitriol, and alendronate in corticosteroid-treated premenopausal patients with systemic lupus erythematosus

Yeap SS, Fauzi AR, Kong NC, Halim AG, Soehardy Z, Rahimah I, et al.

J Rheumatol, 2008 Dec;35(12):2344-7.
PMID: 19004038 DOI: 10.3899/jrheum.080634

OBJECTIVE: To assess bone mineral density (BMD) changes in patients with systemic lupus erythematosus (SLE) undergoing longterm therapy with corticosteroids (CS) while taking calcium, calcitriol, or alendronate. The primary endpoint was BMD changes at 2 years.
METHODS: Premenopausal SLE patients were randomized into 3 groups according to medication: calcium carbonate 500 mg bd (calcium alone), calcitriol 0.25 microg bd plus calcium carbonate 500 mg bd (calcitriol + calcium), and alendronate 70 mg/week plus calcium carbonate 500 mg bd (alendronate + calcium). BMD was measured at baseline and at the end of the first and second years.
RESULTS: Ninety-eight patients were recruited. There were 33 patients taking calcium alone, 33 calcitriol + calcium, and 32 alendronate + calcium. On randomization, median duration of CS use was 2.5 years (range 0-20 yrs). Seventy-seven patients (78.6%) completed the study (23 taking calcium alone, 27 calcitriol + calcium, 27 alendronate + calcium). There were no significant differences in mean CS dosages among the 3 groups at the time of BMD measurements. After 2 years, there were no significant changes in BMD in the calcium-alone and calcitriol + calcium groups, apart from a 0.93% (p < 0.001) reduction in total hip BMD in the calcium-alone group. In contrast, the alendronate + calcium group showed significant increases in BMD of 2.69% (p < 0.001) in the lumbar spine and 1.41% (p < 0.001) in total hip.
CONCLUSION: Both calcium alone and calcitriol + calcium preserved lumbar spine BMD in premenopausal patients with SLE taking longterm CS at 2 years, whereas alendronate + calcium led to increases in BMD in lumbar spine and total hip. Premenopausal women taking CS should be considered for osteoporosis prophylaxis.
Study site: Outpatient clinics in 2 teaching hospitals in Kuala Lumpur, Malaysia

Matched MeSH terms: Osteoporosis/chemically induced
Vitamin D levels: its relationship to bone mineral density response and disease activity in premenopausal Malaysian systemic lupus erythematosus patients on corticosteroids

Yeap SS, Othman AZ, Zain AA, Chan SP

Int J Rheum Dis, 2012 Feb;15(1):17-24.
PMID: 22324943 DOI: 10.1111/j.1756-185X.2011.01653.x

AIM: To determine if baseline vitamin D levels would influence the gain in bone mineral density (BMD) in female systemic lupus erythematosus (SLE) patients on corticosteroids (CS) taking bone-active medication.

METHOD: Premenopausal SLE patients participating in a trial assessing the efficacy of calcium alone, calcitriol and calcium, and alendronate and calcium, on BMD in patients on CS, were studied. Patients were randomly allocated to the treatment groups at the start of the study and followed up for 2 years. Serum 25-hydroxy vitamin D [25(OH)D] was measured at baseline.

RESULTS: Thirty-eight patients were studied. One (2%) patient had osteoporosis, nine (24%) had osteopenia and all others had normal BMD. The mean baseline 25(OH)D levels were 21.6 ± 4.6 ng/mL (± 1 SD). Twelve (32%) patients had vitamin D deficiency [25(OH)D < 20 ng/mL]. There was a significant negative correlation between SLEDAI scores and 25(OH)D levels, that is, patients with high SLEDAI scores had significantly lower 25(OH)D levels (P = 0.033). Left femoral neck BMD was significantly lower in the deficient compared to insufficient group (P = 0.042). There was a trend toward better BMD gain at 2 years in the vitamin D insufficient compared to the deficient group, which did not reach statistical significance.

CONCLUSION: This study showed that in female SLE patients, low vitamin D levels are associated with higher disease activity and suggests that patients who have higher vitamin D levels have a better BMD response during treatment with bone-active agents.

Matched MeSH terms: Osteoporosis/chemically induced*
Piper sarmentosum prevents glucocorticoid-induced osteoporotic bone resorption by increasing 11β-hydroxysteroid dehydrogenase type 1 activity

Suhana MR, Farihah HS, Faizah O, Nazrun SA, Norazlina M, Norliza M, et al.

Clin Ter, 2011;162(4):313-8.
PMID: 21912818

Osteoporosis is a proven complication of long-term glucocorticoid therapy. Concern on glucocorticoid induced osteoporosis has increased dramatically in recent years with the widespread use of synthetic glucocorticoids. Glucocorticoid action in bone depends upon the activity of 11βhydroxysteroid dehydrogenase type 1 enzyme (11βHSD1). This enzyme plays an important role in regulating corticosteroids by locally interconverting cortisone into active cortisol. This has been demonstrated in primary cultures of human, mouse or rat osteoblasts. Therefore, inhibition of this enzyme may reduce bone resorption markers. Piper sarmentosum (Ps) is a potent inhibitor of 11βHSD1 in liver and adipose tissue. In this study we determined the effect of Ps on 11βHSD1 activity in bones of glucocorticoid-induced osteoporotic rats.

Matched MeSH terms: Osteoporosis/chemically induced
Glycyrrhizic acid (GCA) as 11β-hydroxysteroid dehydrogenase inhibitor exerts protective effect against glucocorticoid-induced osteoporosis

Ramli ES, Suhaimi F, Asri SF, Ahmad F, Soelaiman IN

J. Bone Miner. Metab., 2013 May;31(3):262-73.
PMID: 23274351 DOI: 10.1007/s00774-012-0413-x

Rapid onset of bone loss is a frequent complication of systemic glucocorticoid therapy which may lead to fragility fractures. Glucocorticoid action in bone depends upon the activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). Regulations of 11β-HSD1 activity may protect the bone against bone loss due to excess glucocorticoids. Glycyrrhizic acid (GCA) is a potent inhibitor of 11β-HSD. Treatment with GCA led to significant reduction in bone resorption markers. In this study we determined the effect of GCA on 11β-HSD1 activity in bones of glucocorticoid-induced osteoporotic rats. Thirty-six male Sprague-Dawley rats (aged 3 months and weighing 250-300 g) were divided randomly into groups of ten. (1) G1, sham operated group; (2) G2, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral vehicle normal saline vehicle; and (3) G3, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral GCA 120 mg/kg/day The results showed that GCA reduced plasma corticosterone concentration. GCA also reduced serum concentration of the bone resorption marker, pyridinoline and induced 11β-HSD1 dehydrogenase activity in the bone. GCA improved bone structure, which contributed to stronger bone. Therefore, GCA has the potential to be used as an agent to protect the bone against glucocorticoid induced osteoporosis.

Matched MeSH terms: Osteoporosis/chemically induced*
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/chemically induced*
Cost-effectiveness of bisphosphonates for prevention of fracture related to glucocorticoid-induced osteoporosis in Malaysia

Mohd-Tahir NA, Thomas P, Mohamed-Said MS, Makmor-Bakry M, Li SC

Int J Rheum Dis, 2018 Mar;21(3):647-655.
PMID: 29105349 DOI: 10.1111/1756-185X.13206

INTRODUCTION: Glucocorticoid therapy is associated with an appreciable risk of bone loss leading to fractures that require expensive treatments. This study aimed to evaluate the cost-effectiveness of bisphosphonates for prevention of hip fracture in glucocorticoid-induced osteoporosis (GIOP) in Malaysia.

METHOD: Retrospective data were collected from GIOP patients referred to the Universiti Kebangsaan Malaysia Medical Centre. Fracture events and direct medical costs were compared between bisphosphonates and calcium/vitamin D combination.

RESULTS: Fracture events were reported in 28 out of 93 included patients, with hip and vertebral fractures representing 42.9% and 35.7%, respectively. Overall, the use of bisphosphonates could not be considered cost-effective for treatment of all GIOP patients. The presence of certain fracture risk factors was able to modify the cost-effectiveness of bisphosphonates. Bisphosphonates was considered cost-effective if started in patients more than 60 years old. However, the use of bisphosphonates was not cost-effective in GIOP patients with secondary osteoporosis. The incremental cost-effectiveness ratios (ICER) of bisphosphonates in patients with risk factors of previous fracture or rheumatoid arthritis were Malaysian Ringgits (MYR) 108 603.40 and MYR 25 699.21, respectively.

CONCLUSION: Fracture risk factors of age, previous fracture, rheumatoid arthritis and secondary osteoporosis may modify the cost-effectiveness outcomes of bisphosphonates. Bisphosphonates would be considered cost-effective in patients more than 60 years old as compared to calcium/vitamin D treatments. Further evaluation of the impact of fracture risk factors in larger populations would provide more precise information to better assist rational and economical use of anti-osteoporosis treatment in GIOP patients.

Matched MeSH terms: Osteoporosis/chemically induced

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