Appendix 4.

DRUG CHART

Drug	Dosage	Route	Position in therapy	Vertebral*	Hip*	Non- vertebral*	Precautions
Alendronate	5/10 mg daily	Oral	1st line	Yes, 50%	Yes, 51-56%	Yes, 49%	Hypocalcemia, Vitamin D status, should not be used in patients with eGFR below 30 ml/min, pregnancy, lactation, pediatric, ONJ, AFF
	35/70 mg weekly
	150 mg monthly
Risedronate	5 mg daily	Oral	1st line	Yes, 41-49%	Yes, 30%	Yes, 36%	Hypocalcemia, Vitamin D status, should not be used in patients with eGFR below 30 ml/min, pregnancy, lactation, pediatric, ONJ, AFF
	35 mg weekly
	150 mg monthly
Zoledronate	5 mg	IV	1st line	Yes, 70%	Yes, 41%	Yes, 25%	Hypocalcemia, Vitamin D status, should not be used in patients with eGFR below 30 ml/min, pregnancy, lactation, pediatric, ONJ, AFF
Teriparatide	20 mcg	SC	For severe osteoporosis	Yes, 65%	Insufficient data	Yes, 53%	Hypocalcemia, Vitamin D status, Hypersensitivity, local tissue damage, pregnancy, lactation, pediatric,
Denosumab	60 mg	SC	1st line	Yes, 68%	Yes, 40%	Yes, 20%	Hypocalcemia, Vitamin D status, pregnancy, lactation, pediatric,
MHT	Various regimes	Various regimes	1st line with menopausal symptoms (<10 years menopause)	Yes, 30-70%	Yes, 40%	Yes, 27%	Blood clots, Cancer (such as breast, uterine, or endometrial), Heart or liver disease, Heart attack, Known or suspected pregnancy, Stroke
Raloxifene	60 mg	Oral	At risk of breast cancer, without Vasomotor symptoms, <10 years menopause	Yes, 40%	No	No	With a low risk of DVT and for whom bisphosphonates or denosumab are not appropriate, or with a high risk of breast cancer
Tibolone	2.5 mg	Oral	1st line <10 years menopause	Yes, 50%	Yes, 26%	Yes, 26%	To stop tibolone a few weeks before any operation to reduce the risk of a blood clot, drug interaction with warfarin
Calcitonin	200 IU	Nasal spray	2nd line	Yes, 21%	No	No	Serious hypersensitivity reactions, including fatal anaphylaxis, reported; consider skin testing prior to treatment
Drug	Advantages	Disadvantages		Contraindications			Adverse effects
Alendronate	Most commonly used drug	Inconvenient administration - Stay upright for 30 min on intake, drink lots of water, no food before taking the drug, drug holiday may be needed after 3-5 years		Hypocalcemia, Hypersensitivity, Compromised renal function, Upper GI disease - Abnormalities of the esophagus which delay esophageal emptying such as stricture of achalasia, patients at increased risk of aspiration			Dyspepsia, esophagitis abdominal pain, musculoskeletal pain
Risedronate		Inconvenient administration - Stay upright for 30 min on intake, drink lots of water, no food before taking the drug, drug holiday may be needed after 3-5 years anaphylaxis, including fatal events		Hypocalcemia, hypersensitivity, compromised renal function, Upper GI disease - Abnormalities of the esophagus which delay esophageal emptying such as stricture of achalasia, patients at increased risk of aspiration			Rash, abdominal pain, dyspepsia, diarrhea, arthralgia
Zoledronate	1st line drug,			Hypocalcemia, hypersensitivity, compromised renal function			Acute reaction (flu such as symptoms, fever, myalgia) may occur within 3 days of infusion, hypotension, fatigue, eye inflammation, more nausea, vomiting, abdominal pain
Teriparatide	Potent bone forming activity, Large increase in spine BMD over 2 years	Reserved line drug, 2 years usage, daily injections required,		Hypocalcemia, hypersensitivity			Headache, hypercalcemia (high-quality); hypercalciuria, renal adverse effects, nausea, rhinitis, arthralgia
Denosumab	1st line drug, Rise of BMD reported over 10 years at spine, hip and nonvertebral sites, can be used in patients in eGFR 15-30 ml/min	Loss of effect and drop in BMD after discontinuation (should be continued on bisphosphonates)		Hypocalcemia, Hypersensitivity			Dermatitis, rash, mild bone/muscle pain, UTIs
MHT	Less musculoskeletal symptoms of aches and pains and possibly sarcopenia (or muscle wasting)	breast cancer VTE, stroke, potentiation of preexisting breast cancer, increased risk of gall stones, depression, headache, premenstrual syndrome, breast tenderness, skin irritation, weight gain, menstrual bleeding		Active endometrial and gynecological hormone- dependent cancers Active breast cancer, Undiagnosed, abnormal vaginal bleeding Moderate and high risk for breast cancer Established CVD and at severe increased risk of CVD, Previous personal or family history of venous thromboembolism Systematic lupus erythematous, Diabetes with end organ disease Severe active liver disease with impaired or abnormal liver function x Previous personal or family history of venous thromboembolism x Known or suspected pregnancy			Bloating, Breast swelling or tenderness, Headaches, Mood changes, Nausea, Vaginal bleeding
Raloxifene	benefit of a reduced incidence of invasive estrogen receptor-positive breast cancer both during treatment and for at least 5 years after completion	Daily oral administration		Pregnancy, lactation, Active history of thromboembolic disorders			Venous thromboembolism, stroke
Tibolone	Increases BMD, decreases cholesterol and triglycerides similar to conventional MHT	Reduction of HDL levels and its high cost		Pregnancy and lactation, breast cancer, estrogen-dependent malignant tumors (e.g., endometrial cancer) Undiagnosed genital bleeding, Untreated endometrial hyperplasia, venous thromboembolism (deep venous thrombosis pulmonary embolism, thrombophilic disorders, arterial thromboembolic disease (e.g., angina, myocardial infarction, stroke or TIA), Acute liver disease, or a history of liver disease, Hypersensitivity to the active substance(s), Porphyria			May increase stroke rates in women over 60 years of age, Weight gain, Unscheduled bleeding
Calcitonin	Ease of administration	Circulating antibodies to calcitonin-salmon may develop, and may cause loss of response to treatment		Hypersensitivity to calcitonin-salmon			Rhinitis, epistaxis, and allergic reactions

*% reduction in fracture in individual pivotal studies only and not in head-head studies. eGFR: Estimated glomerular filtration rate, HDL: High-density lipoprotein, BMD: Bone mineral density, DVT: Deep vein thrombosis, GI: Gastrointestinal, MHT: Menopause hormone therapy, TIA: Transient ischaemic attack, ONJ: Osteonecrosis of the jaw