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Drug delivery systems for prevention and treatment of osteoporotic fracture

Shuid AN, Ibrahim N', Mohd Amin MC, Mohamed IN

Curr Drug Targets, 2013 Dec;14(13):1558-64.
PMID: 24200294

Anti-osteoporotic drugs are available for treatment of osteoporosis and for preventing osteoporosis complications especially fractures. Most of the current anti-osteoporotic drugs are administered orally or parenterally to target the osteoporosis-affected bones. However, bone is a peripheral organ with limited blood supply. Therefore, the drugs delivered are exposed to various physicochemical and biological factors which affect the bioavailability of the drugs. In preclinical research, the dose of a potential anti-osteoporotic agent used in animal model may be too high for human application when administered via the conventional route of administration. The current anti-osteoporotic drugs need to be administered at higher doses to account for pharmacological interactions. However, this will expose the patients to adverse effects such as the cancer risks of postmenopausal women who took estrogen replacement therapy. There is also problem with patient compliance as anti-osteoporotic drugs may have to be taken for prolonged duration. The current deliveries of drugs need to be improved to overcome these problems. This review discussed several potential drug delivery systems which are able to contain the anti-osteoporosis drugs and release them slowly to the targeted bone. Among them are various carriers, polymers and microsponges, which may not only increase drug efficacy but also reduce adverse effects. The delivery systems allow the drugs to be administered locally at the targeted bone for longer duration, therefore reducing drug frequency and improving patient's compliance. It is hoped that these delivery systems may be applicable for the treatment of osteoporosis in the future to keep tab of the rising osteoporotic fracture incidence.

Matched MeSH terms: Osteoporotic Fractures/drug therapy*
A review on the use of statins and tocotrienols, individually or in combination for the treatment of osteoporosis

Abdul-Majeed S, Mohamed N, Soelaiman IN

Curr Drug Targets, 2013 Dec;14(13):1579-90.
PMID: 23848479

Skeletal tissue undergoes continuous remodeling which makes it unique among other body tissues. Osteoporosis is a common bone metabolic disorder affecting both men and women. Osteoporosis and its complications mainly osteoporotic fractures, have a high impact on health and economy. Current approved medications are associated with numerous side effects, which limit their use. Identification of a new and safe therapy is mandatory. Statins, also known as HMGCoA reductase inhibitors, are frequently used for the treatment of hypercholesterolemia and for the prevention of morbidity and mortality associated with cardiovascular disease. Statins improved bone health status in intact and ovariectomised rodents following high clinically intolerable oral doses. However, this beneficial effect of statins could not be significantly demonstrated in humans. The reason behind this discrepancy might be due to the safety and bioavailability of the currently used oral statins. Vitamin E, especially the tocotrienols at the dose 60 mg/kg/day provided significant antiosteoporotic effects in different animal models of osteoporosis. The use of the aforementioned dose of tocotrienols was shown to be safe in both humans and animals. Enhancement of bone formation and reduction of bone resorption were achieved more effectively by a combination of tocotrienols and statins than by either treatment when supplemented separately at clinically tolerable doses. Therefore, the adverse effects associated with high statin doses might be avoided with the coadministration of tocotrienols. Moreover, the combination therapy strategy might be useful for patients who are at high risk of osteoporosis, cardiovascular events and hypercholesterolaemia.

Matched MeSH terms: Osteoporotic Fractures/drug therapy
Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study

Estai MA, Suhaimi FH, Das S, Fadzilah FM, Alhabshi SM, Shuid AN, et al.

Clinics (Sao Paulo), 2011;66(5):865-72.
PMID: 21789393

INTRODUCTION: Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties.
OBJECTIVES: To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state.
METHODS: A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment.
RESULTS: The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 ± 11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 ± 4.05, 22.4 ± 4.14 and 17.5 ± 3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05).
CONCLUSION: The Piper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states.

Matched MeSH terms: Osteoporotic Fractures/drug therapy*
Update on statins: hope for osteoporotic fracture healing treatment

Ibrahim N', Mohamed N, Shuid AN

Curr Drug Targets, 2013 Dec;14(13):1524-32.
PMID: 23876090

Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.

Matched MeSH terms: Osteoporotic Fractures/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: Osteoporotic Fractures/drug therapy