Bones are constantly being remodelled by osteoclast and osteoblast activity. Osteoclasts are cells which break down old bone tissue and osteoblasts are cells that create bone tissue. Bones become weaker with age and some people will develop osteoporosis, which is a health condition that weakens bones, making them fragile and more likely to break. Osteoporosis is common in postmenopausal women but can also be induced following treatment with glucocorticoids. The disease is characterised by loss of bone density and structural deterioration. Treatment options for osteoporosis will be explored in this article, alongside their pharmacokinetic properties, adverse effects, cautions and contraindications and common interactions. Non-pharmacological management strategies to treat osteoporosis include physical activity which helps to maintain bone density. Furthermore, patients should be advised to maintain a balanced diet including adequate intake of calcium and vitamin D. Where relevant, patients should also be advised to stop smoking and reduce alcohol intake as this can help reduce the risk of developing osteoporosis. Adobe stock images Fig 1: Human Bone Remodelling Cycle Pharmacological Management Bisphosphonates Bisphosphonates inhibit osteoclastic bone resorption by binding strongly to bone mineral at the site of bone resorption. When the bisphosphonate bound bone is resorbed by osteoclasts, bisphosphonate is released which impairs the ability of the osteoclast to adhere to the surface of the bone. Therefore, bisphosphonates slow down turnover of bone by inhibiting reabsorption by osteoclasts. Bisphosphonates have no effect on bone formation. Oral bisphosphonates include alendronic acid, risedronate sodium and ibandronic acid. Zolendronic acid and ibandronic acid are available as an infusion. Pharmacokinetics Absorption of oral bisphosphonates can be reduced by food, drinks and some medications. It should therefore be taken at least 30 minutes before food, drink and other medications. Bisphosphonates are not metabolised and are excreted via the kidneys. Half-life of bisphosphonates is expected to be more than 10 years meaning doses are often weekly or sometimes yearly (zolendronic acid). Contraindications and Cautions Poor renal function (CKD 3b and below) Abnormalities of the oesophagus Hypocalcaemia – calcium and vitamin D should be corrected if necessary before treatment commences Pregnancy and breastfeeding Adverse Effects and Counselling Points Patients must take oral bisphosphonates with a glass of water and remain upright for 30 minutes following administration to prevent oesophageal irritation. Treatment is usually recommended for 5-10 years. Some patients will be offered a drug holiday to minimise the risk of atypical femoral fractures observed with long-term use. Patients initiated on bisphosphonates should be counselled on the risk of: Atypical femoral fractures Osteonecrosis of the jaw Osteonecrosis of the external auditory canal Interactions Antacids and calcium supplements – absorption of oral bisphosphonates is decreased when co-administered with antacids or calcium supplements. Oral bisphosphonates should be taken 30 minutes before antacids or calcium supplements. Concomitant use with NSAIDS increase the risk of gastrointestinal irritation Denosumab Denosumab is a human monoclonal antibody. It works by binding to the ligand RANKL, thus preventing this from binding to and activating RANK receptors on the osteoclast surface. By inhibiting activation of RANK, osteoclast formation is inhibited. Adobe stock images Fig 2: Denosumab, a human monoclonal antibody to treat osteoporosis Contraindications and Cautions <18 years old Hypocalcaemia Hypersensitivity to the active substance Adverse Effects and Counselling Points Cessation of denosumab can lead to rebound increase of bone turnover. Patients should be advised not to stop denosumab unless told to do so by a healthcare professional. Patients initiated on denosumab should be counselled on the risk of Atypical femoral fractures Osteonecrosis of the jaw Hypocalcaemia, symptoms include muscle spasms, twitches, cramps, numbness or tingling in the fingers, toes, or around the mouth Interactions Cinacalcet – increased risk of hypocalcaemia Etelcalcetide – increased risk of hypocalcaemia Raloxifene Raloxifene is a selective oestrogen receptor modulator. It provides the benefits that oestrogen provides to the bone without causing negative effects on endometrial and breast tissue. This medication is only used to treat osteoporosis in postmenopausal women. Contraindications and Cautions History of VTE Hepatic impairment Severe renal impairment Women of childbearing potential Unexplained uterine bleeding Adverse Effects and Counselling Points Raloxifene may cause leg cramps, oedema and vasodilation. Due to its effects on oestrogen, it may also increase the risk of venous thromboembolism Interactions Combined or contraceptives – may reduce efficacy of raloxifene Hormone replacement therapy – may reduce efficacy of raloxifene Strontium ranelate Strontium is an alkaline earth metal. Its mechanism of action is not fully understood but it is thought to demonstrate some antiresorptive effect by acting as a substitute for calcium. Strontium is excreted unchanged by the kidney and gastrointestinal tract. The manufacturer recommends that treatment with strontium is avoided in severe renal impairment. Contraindications and Cautions Cerebrovascular disease Venous thromboembolism current or historic Ischaemic heart disease, peripheral artery disease Uncontrolled hypertension and immobilisation Adverse Effects Strontium may cause nausea and diarrhoea. Interactions Fluoroquinolones – absorption of fluoroquinolones may be decreased by strontium Tetracyclines – absorption of tetracyclines may be decreased by strontium Teriparatide Teriparatide is the active component of endogenous parathyroid hormone. It works by directly stimulating formation of bone through upregulation of growth factors that increase osteoblast survival. It also works indirectly by increasing absorption of calcium from the intestine and reabsorption of calcium via the kidneys. Teriparatide can only be given for a maximum of 24 months as the efficacy and safety data beyond 2 years of treatment with teriparatide is limited. Contraindications and Cautions Pregnancy and breastfeeding Hypercalcaemia Severe renal impairment, metabolic Bone disease other than osteoporosis or steroid-induced osteoporosis Raised ALP Skeletal malignancy or bone metastases Previous external beam or implant radiation therapy to the skeleton. Adverse Effects and Counselling Points May cause slight elevation in calcium levels following administration. If serum calcium is measured it should be done a minimum of 16 hours following the most recent teriparatide injection Maximum duration 24 months References BNF summary of osteoporosis available from: Osteoporosis – prevention of fragility fractures | Health topics A to Z | CKS | NICE. Accessed 16/12/24 SPC Alendronic acid 70mg tablets. Last updated on emc: 28 Apr 2022. Available from Alendronic Acid 70 mg tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk). Accessed 16/12/24 Online BNF Alendronic acid available from Alendronic acid | Drugs | BNF | NICE. Accessed 16/12/24 SPC Prolia 60mg solution for injection pre-filled syringe. Last updated on emc: 21 Nov 2024. Avaialble from Prolia 60 mg solution for injection in pre-filled syringe – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk). Accessed 16/12/24 Online BNF Denosumab available from: Denosumab | Drugs | BNF | NICE. Accessed 16/12/24 Online BNF Strontium ranelate available from: Strontium ranelate | Drugs | BNF | NICE. Accessed 16/12/24 Online BNF Raloxifene available from Raloxifene hydrochloride | Drugs | BNF | NICE Accessed 18/12/24 SPC Raloxifene hydrochloride 60mg film-coated tablets. Last updated on emc: 25 Jun 2019. Available from Raloxifene hydrochloride 60mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) Accessed 18/12/24 Online BNF Teriparatide available from Teriparatide | Drugs | BNF | NICE. Accessed 19/12/2024 SPC Forsteo 20microgram/80microlitres solution for injection in pre-filled pen. Last updated on emc: 06 Feb 2023. Available from Forsteo 20 micrograms/80 microlitres solution for injection in pre-filled pen – Summary of Product Characteristics (SmPC) – (emc). Accessed 19/12/2024 National Osteoporosis Guideline Group UK. Available from Section 6: Pharmacological treatment options | NOGG. Accessed 18/12/24 Lindsay. R, et al. (2016). Teriparatide for osteoporosis: importance of the full course. Osteoporosis International. Available at: Teriparatide for osteoporosis: importance of the full course – PMC. Accessed 19/12/2024 Saag KG, Zanchetta JR, Devogelaer JP, et al. Effects of teriparatide versus alendronate for treating glucocorticoid‐induced osteoporosis: thirty‐six‐month results of a randomized, double‐blind, controlled trial. Arthritis Rheum. 2009;60:3346‐3355. [DOI] [PubMed] [Google Scholar] Do you think you’re ready? Take the quiz below Pro Feature - Quiz Drugs For Osteoporosis Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Rate This Article