Osteoporosis
Clinical Snapshot
Osteoporosis is a skeletal disorder in which bone strength is compromised — through low bone mass and disrupted bone microarchitecture — leading to an increased risk of fracture from forces that would not break normal bone.[1] Bone is in constant remodelling: osteoclasts resorb old bone and osteoblasts lay down new bone in a tightly coupled cycle. When resorption outpaces formation, as happens progressively with age and accelerates sharply after menopause, the result is net bone loss. Because bone loss itself is silent, osteoporosis usually first becomes apparent as a fragility fracture — a fracture from a fall from standing height or less — or as incidental vertebral height loss found on imaging, which is why systematic risk-based screening matters more than waiting for symptoms. The current standard of care in Canada is the 2023 Osteoporosis Canada clinical practice guideline, a substantial update of the 2010 guideline: it replaced the older low/moderate/high three-tier risk categories with a hybrid FRAX-or-CAROC-plus-BMD-and-age treatment threshold, revised the recommended calcium and vitamin D intake downward toward Health Canada's general population targets, and set explicit, agent-specific rules for bisphosphonate drug holidays and denosumab discontinuation.[1]
Recognize the Condition
Typical presentation
Osteoporosis itself is asymptomatic — there is no pain or symptom from low bone density alone. It typically comes to clinical attention in one of three ways: a fragility fracture (hip, spine, wrist, humerus, pelvis, or another major site) occurring from a fall from standing height or less, or with no identifiable trauma at all; incidentally recognized vertebral height loss or wedging on an imaging study obtained for another reason; or proactive risk-based BMD screening in an asymptomatic patient who meets age or risk-factor criteria.
Vertebral compression fracture
The most common osteoporotic fracture, and frequently asymptomatic at the time it occurs. When symptomatic, it presents as sudden-onset mid-back pain, often after a minor trauma such as bending, lifting, or coughing, that may radiate around the trunk. Progressive height loss and increasing kyphosis (a "dowager's hump") reflect the cumulative effect of multiple vertebral fractures over time.
Physical findings suggesting an undiagnosed vertebral fracture
- Measured height loss exceeding 2 cm within the past year, or more than 6 cm from documented or recalled peak adult height.
- Kyphosis — a rib-to-pelvis distance of less than 3 finger-breadths on examination.
- Occiput unable to touch the wall when standing with heels and back against it.
- New or worsening chronic back pain without another clear cause.
Primary vs. secondary osteoporosis
Primary osteoporosis
Age-related and postmenopausal bone loss with no other identifiable cause — the focus of this chapter and of the 2023 Osteoporosis Canada guideline.
Secondary osteoporosis
Bone loss driven by an identifiable endocrine, gastrointestinal, renal, rheumatologic, hematologic, or medication-related cause (see Risk factors). Secondary osteoporosis is more likely in a young patient, a man, or anyone whose bone loss or fracture is out of proportion to age and risk-factor burden — investigate and treat the underlying cause in addition to standard osteoporosis therapy.
Risk Factors
Conditions associated with increased fracture risk
- Age 65 years or older.
- Previous fragility fracture at any age — a fracture from a fall from standing height or less.
- Parental history of hip fracture.
- Osteopenia identified on x-ray.
- Current smoking.
- High alcohol intake (3 or more drinks per day).
- Low body weight (under 60 kg) or major weight loss (more than 10% of body weight since age 25).
- Body mass index under 20.
- One or more falls in the past 12 months.
- Hypogonadism or premature menopause (before age 45).
- Hyperthyroidism.
- Cushing syndrome.
- Primary hyperparathyroidism.
- Chronic kidney disease.
- Organ transplantation.
- Gastrointestinal disease: gastric or bariatric surgery, malabsorption syndromes, inflammatory bowel disease, celiac disease.
- Rheumatoid arthritis and other inflammatory conditions strongly associated with rapid bone loss.
- Multiple myeloma and other conditions causing secondary osteoporosis.
Medications associated with increased fracture risk
- Glucocorticoids, taken long-term (see Special populations for the specific dose/duration threshold).
- Androgen deprivation therapy.
- Aromatase inhibitors.
- Anticoagulants — unfractionated heparin, low-molecular-weight heparin, and warfarin.
- Antiepileptic drugs, particularly valproic acid and enzyme-inducing agents.
- Antiretroviral therapy.
- Chemotherapy.
- Cyclosporine and other calcineurin inhibitors.
- Loop diuretics.
- Proton pump inhibitors, with prolonged use.
- Selective serotonin reuptake inhibitors (SSRIs).
- Thiazolidinediones.
- High-dose vitamin A.
- Drugs that increase fall risk in older adults — antipsychotics, benzodiazepines, and other sedative-hypnotics.
Red Flags & Refer
The following presentations need urgent workup rather than routine osteoporosis management:
- A hip or vertebral fracture after menopause or age 50 — this is itself diagnostic of osteoporosis regardless of BMD and should trigger immediate risk assessment and treatment planning, not a wait for a DXA appointment.
- Acute severe back pain with height loss, especially with fever, unexplained weight loss, a personal history of cancer, a new neurologic deficit, or pain that is progressive and unremitting rather than mechanical — these suggest a pathologic (malignant or infectious) fracture rather than a simple osteoporotic one and need urgent imaging and oncology/hematology or infectious-disease input.
- Multiple or atypical fractures at unusual sites with minimal trauma — consider a secondary cause or malignancy rather than assuming primary osteoporosis.
- New thigh or groin pain, unilateral or bilateral, in a patient on long-term (generally 2 or more years) bisphosphonate or denosumab therapy — evaluate urgently for an atypical femoral fracture with plain x-rays; stop the antiresorptive agent and refer to orthopedic surgery immediately if imaging shows an impending or incomplete fracture.[2]
- Suspected osteonecrosis of the jaw (persistent oral pain, exposed bone, non-healing socket) in a patient on a bisphosphonate or denosumab, especially after a dental extraction or implant — refer to oral surgery/dentistry.
- Severe or symptomatic hypocalcemia (perioral tingling, muscle cramps or spasm, seizure) after a zoledronic acid infusion or a denosumab dose — urgent evaluation and calcium correction.
- A new fracture, or a substantial BMD decline, in a patient who is adherent to therapy — refer for reassessment rather than assuming the fracture proves the drug has failed.
Assessment & Diagnosis
Distinguishing a fragility fracture from a pathologic fracture
Most vertebral and hip fractures in an older adult with known risk factors are osteoporotic. Specific features should prompt evaluation for malignancy, infection, or another non-osteoporotic cause before attributing a fracture to osteoporosis alone.
| Feature | Favors an osteoporotic fragility fracture | Favors a pathologic/non-osteoporotic cause |
|---|---|---|
| Trauma level | Fall from standing height or less, or no identifiable trauma | Any fracture where pain is disproportionate to the trauma described |
| Age | Postmenopausal woman, or a man over 50 | Under 50 without a clear secondary cause |
| Pain pattern | Improves over weeks; mechanical, worse with activity | Progressive and unremitting; worse at night or at rest |
| Systemic features | Absent | Fever, unexplained weight loss, night sweats |
| History | No cancer history; known osteoporosis risk factors | Personal history of cancer, especially breast, prostate, lung, renal, thyroid, or multiple myeloma |
| Neurologic findings | Absent | New focal deficit, or cord/cauda equina signs |
| Laboratory findings | Normal CBC, calcium, alkaline phosphatase, creatinine | Anemia, elevated calcium, abnormal serum/urine protein electrophoresis, or alkaline phosphatase elevated out of proportion to fracture healing |
Any combination of the pathologic-cause features above should prompt further workup — imaging, oncology or hematology referral, biopsy as indicated — before or alongside starting osteoporosis therapy.
History
- Ask specifically about height loss (more than 6 cm from peak adult height, or more than 2 cm within the past year), falls in the past 12 months, and any prior fracture and its mechanism.
- Screen for the conditions and medications listed under Risk factors, and ask about glucocorticoid exposure specifically — dose, duration, and indication.
- Ask about dietary calcium intake, sun exposure and vitamin D intake, smoking, and alcohol intake.
Physical examination
- Measured height, weight, and body mass index; compare current height with documented or recalled peak adult height.
- Rib-to-pelvis distance (kyphosis screen) and occiput-to-wall distance.
- Gait, balance, and lower-limb strength (e.g., ability to rise from a chair without using the arms) as a fall-risk screen.
Laboratory investigations
- CBC, calcium (corrected for albumin), phosphate, creatinine, and alkaline phosphatase in every patient being assessed for osteoporosis — all should be normal in primary osteoporosis; an abnormality points toward a secondary cause.
- TSH if there is clinical suspicion of thyroid disease.
- Serum protein electrophoresis in a patient with a vertebral fracture, to screen for myeloma.
- Serum 25-hydroxyvitamin D only in a patient with risk factors for deficiency (malabsorption, housebound, established osteoporosis about to start pharmacotherapy) — not a routine test in every patient, and not to be rechecked sooner than 3 months after starting supplementation.
- Bone turnover markers are not appropriate for diagnosis or routine management and should not be ordered as part of a standard osteoporosis workup.[1]
Imaging
- Lateral thoracic and lumbar spine radiographs, or a vertebral fracture assessment by DXA, to screen for an undiagnosed vertebral fracture when there is clinical evidence suggestive of one (height loss, kyphosis, unexplained back pain), when the 10-year FRAX major osteoporotic fracture risk is 15-19%, or in anyone 65 or older with a T-score of -2.5 or lower.[1]
- Plain x-ray is used to confirm a suspected fracture; a bone scan can identify new fracture activity in a patient with back pain and no obvious fracture on x-ray.
Bone mineral density testing
Dual-energy x-ray absorptiometry (DXA) of the spine and hip is the preferred method of measuring bone mass, both to estimate fracture risk and to monitor response to therapy. Bone mineral density is reported as a T-score — the number of standard deviations above or below the mean BMD of a young adult reference population.
| T-score | Category |
|---|---|
| -1.0 or higher | Normal bone density |
| Between -1.0 and -2.5 | Osteopenia (low bone mass) |
| -2.5 or lower | Osteoporosis |
| -2.5 or lower, plus one or more fragility fractures | Severe (established) osteoporosis |
Suggest BMD testing in postmenopausal females and males who are 50-64 years old with a previous fragility fracture or 2 or more clinical risk factors, who are 65 or older with 1 clinical risk factor, or who are 70 or older regardless of risk factors.[1]
Fracture risk assessment tools
BMD alone is an incomplete predictor of fracture risk — a fracture risk calculator that combines BMD with clinical risk factors performs better and now drives the treatment decision directly, rather than the T-score alone.
The Canada-specific FRAX tool is the preferred fracture risk assessment tool.[3] It combines age, sex, weight, height, and a defined set of clinical risk factors with femoral neck BMD (or body mass index, if BMD is unavailable) to estimate the 10-year probability of a major osteoporotic fracture (hip, clinical spine, forearm, or proximal humerus) and of hip fracture specifically. FRAX is a continuously-weighted, multivariable regression model, not a simple point-sum score — precise scoring requires the validated FRAX calculator, not manual estimation. Use the table below to understand which inputs drive the score, then calculate the patient's actual probability using the validated Canada-specific online tool.
| FRAX input | How it is used |
|---|---|
| Age, sex | Continuous variables — risk rises with age |
| Weight, height (or BMI if BMD unavailable) | Continuous variables |
| Previous fragility fracture | Yes/no — substantially raises risk |
| Parent with a hip fracture | Yes/no |
| Current smoking | Yes/no |
| Long-term oral glucocorticoid use | Yes/no — the risk estimate is increased by a further 15% if the prednisone-equivalent dose exceeds 7.5 mg/day |
| Rheumatoid arthritis | Yes/no |
| Secondary osteoporosis (e.g., type 1 diabetes, untreated hyperthyroidism, hypogonadism, malnutrition, chronic liver disease) | Yes/no |
| Alcohol intake of 3 or more units/day | Yes/no |
| Femoral neck BMD (or BMI if unavailable) | Continuous variable |
CAROC (Canadian Association of Radiologists and Osteoporosis Canada tool) is an accepted alternative that uses femoral neck BMD and age as its base, then shifts a patient to a higher risk category for a prior fragility fracture at a site other than hip or spine, or for corticosteroid therapy; 2 such factors, or 1 fracture plus corticosteroid therapy, places a patient in the high-risk category directly.
Treatment Targets
- Prevent first and recurrent fragility fractures, particularly of the hip and spine.
- Preserve or increase bone mineral density.
- Prevent the disability, loss of independence, and mortality associated with fracture, especially hip fracture.
- Ensure adequate calcium and vitamin D status and address fall risk as the foundation for every treatment plan, whether or not pharmacotherapy is also indicated.
- Identify and treat any secondary cause of bone loss alongside standard osteoporosis therapy.
- Reassess fracture risk and bone density on a defined schedule, and revisit the treatment plan — continue, switch, or pause — rather than continuing therapy indefinitely without review.
Choose Initial Treatment
Who to treat
Calculate a 10-year fracture risk using the Canada-specific FRAX tool (preferred) or CAROC in every postmenopausal female or male aged 50 or older being assessed for osteoporosis, and combine it with fracture history and T-score using the thresholds below.[1]
Treatment-initiation thresholds (2023 Osteoporosis Canada guideline)
Recommend starting pharmacotherapy
Previous hip fracture, vertebral fracture, or 2 or more osteoporosis-related fractures; OR a 10-year major osteoporotic fracture risk of 20% or higher; OR age 70 or older with a T-score of -2.5 or lower at the femoral neck, total hip, or lumbar spine.
Suggest starting pharmacotherapy
A 10-year major osteoporotic fracture risk between 15% and 19.9%; OR age under 70 with a T-score of -2.5 or lower at the femoral neck, total hip, or lumbar spine.
Pharmacotherapy not currently indicated
Below both thresholds above — continue calcium/vitamin D adequacy, exercise, and fall-risk reduction, and repeat BMD/fracture-risk assessment on the schedule in Monitoring & follow-up.
1st line for most patients start an oral or IV bisphosphonate — alendronate, risedronate, or zoledronic acid — as initial pharmacotherapy for a patient who meets either treatment threshold above.[1]
Alternative — postmenopausal females under 60 years of age or within 10 years of menopause who also want treatment for vasomotor menopausal symptoms menopausal hormone therapy is a reasonable alternative to a bisphosphonate.[1]
Alternative — bisphosphonate contraindication, intolerance, or a genuine adherence/administration barrier denosumab. Starting it means committing to an uninterrupted long-term dosing schedule, since stopping denosumab carries a real rebound vertebral-fracture risk — see Special populations and the algorithm for the mandatory transition plan.[1][4]
Special situation — a recent severe vertebral fracture, or more than 1 vertebral fracture with a T-score below -2.5 seek advice from an osteoporosis expert on an osteoanabolic agent (teriparatide or romosozumab) as initial therapy, generally followed by an antiresorptive agent to preserve the gains once the anabolic course ends.[1]
Special situation — contraindication or intolerance to the options above, or a patient who declines them but still wants therapy rather than none raloxifene is a reasonable choice, best reserved for a patient at low hip-fracture risk given the lack of nonvertebral/hip fracture-prevention evidence.[1]
Special situation — glucocorticoid-induced osteoporosis stratify fracture risk with FRAX (adding 15% to the calculated risk if the prednisone-equivalent dose exceeds 7.5 mg/day), then treat: an oral bisphosphonate for moderate risk, and an oral or IV bisphosphonate, denosumab, or an osteoanabolic agent for high or very-high risk. Current guidance favors an osteoanabolic agent (teriparatide or romosozumab) as initial therapy specifically in the high/very-high-risk tier — a change from the older approach of defaulting every risk tier to an oral bisphosphonate first.[5]
Non-Pharmacologic Treatment
- Balance and functional training more than twice weekly for all major muscle groups, to reduce fall risk.
- Progressive resistance training more than twice weekly, including exercises that target the back extensor and abdominal muscles.
- At least 150 minutes per week of moderate-to-vigorous physical activity, in addition to — not instead of — the balance, functional, and strength training above.[1]
- In a patient with a known vertebral fracture or very low BMD, avoid high-impact activity and exercises that combine spinal flexion with loading (e.g., toe-touches, full sit-ups) — favor extension-based and low-impact loading instead, and involve physiotherapy for an individualized program.
- Fall-prevention home assessment: remove loose rugs, install grab bars and adequate lighting, correct vision, and review the medication list for drugs that increase fall risk (benzodiazepines, other sedative-hypnotics, antipsychotics).
- Smoking cessation.
- Limit alcohol to fewer than 3 drinks per day.
- Encourage adequate dietary protein alongside calcium and vitamin D — undernutrition and low body weight are independent risk factors for fracture.
- Hip protectors can be considered for frail, high-falls-risk residents of long-term care.
Special Populations
Pregnancy
Osteoporosis pharmacotherapy is not started in pregnancy. Bisphosphonates, denosumab, teriparatide, and romosozumab are all contraindicated or not recommended in pregnancy; bisphosphonates in particular are retained in bone and released gradually for years, so pregnancy should be avoided for a defined period after stopping one, per the product-specific guidance. Continue non-pharmacologic measures — calcium/vitamin D adequacy, exercise, fall prevention — throughout pregnancy. A patient who becomes pregnant while established on osteoporosis pharmacotherapy needs prompt specialist (endocrinology or high-risk obstetrics) involvement rather than simply stopping and restarting later without a plan.
Breastfeeding
Bisphosphonates, denosumab, teriparatide, and romosozumab are not recommended during breastfeeding. Calcium and vitamin D adequacy should continue. Resuming pharmacotherapy after breastfeeding ends should follow a repeat fracture-risk assessment rather than an automatic restart at the pre-pregnancy dose.
Pediatrics
This chapter addresses primary osteoporosis in postmenopausal females and males aged 50 and older, per the scope of the current Canadian guideline. Osteoporosis and low bone density in children and adolescents are a distinct clinical entity with different diagnostic criteria and treatments — refer to a pediatric bone/endocrine specialist rather than extrapolating adult dosing.
Renal impairment
All osteoporosis therapies are acceptable above chronic kidney disease stage 4 (a GFR of 15-29 mL/min is where extra caution begins). Oral and IV bisphosphonates are excreted renally and are generally avoided below a creatinine clearance of 30-35 mL/min, per the product-specific cutoff — see Drug tables for the exact threshold for each agent. Denosumab, estrogen, and SERMs are not renally cleared and are not restricted by renal function in the same way, but denosumab carries a higher hypocalcemia risk in renal impairment and needs closer calcium monitoring. Stage 5 CKD or dialysis-dependent patients need osteoporosis therapy decisions made jointly with nephrology.
Men
Osteoporosis in men is under-recognized and undertreated relative to women, even though vertebral deformities suggestive of fracture occur nearly as often in men as in women, and hip fracture in men carries a higher risk of death or disability than in women. Apply the same risk-assessment and treatment thresholds used for postmenopausal women.
Older adults and frail patients
Falls contribute as much to fracture risk as bone density in this group — prioritize the fall-risk-reduction measures in Non-pharmacologic treatment. An IV or injectable agent (zoledronic acid or denosumab) may be preferable to an oral bisphosphonate when a patient cannot reliably follow the upright/empty-stomach dosing instructions.
Glucocorticoid-induced osteoporosis
The most common secondary cause of osteoporotic fracture. Assess any patient starting or continuing a prednisone-equivalent dose of 2.5 mg/day or more for 3 months or longer with a baseline BMD and a FRAX calculation, adding 15% to the calculated risk if the dose exceeds 7.5 mg/day. Current guidance recommends an osteoanabolic agent (teriparatide or romosozumab) as initial therapy specifically for a patient at high or very-high fracture risk on long-term glucocorticoids, rather than defaulting every risk tier to an oral bisphosphonate as earlier guidance did.[5]
Monitoring & Follow-Up
Repeat BMD testing and fracture-risk assessment 3 years after initiating pharmacotherapy.[1] For a patient who does not meet the treatment threshold or chooses not to start therapy, repeat BMD and fracture-risk assessment at 5-10 years if the 10-year major osteoporotic fracture risk is below 10%, at 5 years if it is 10-15%, or at 3 years if it is 15% or higher, and sooner if a new fracture, new clinical risk factor, or secondary cause emerges in the interim.[1] After a bisphosphonate drug holiday begins, repeat BMD measurement and clinical fracture-risk assessment 3 years later to decide whether to resume therapy.[1] Confirm adherence at every encounter — an oral bisphosphonate's fracture-prevention benefit becomes doubtful once adherence falls below about 80%, and adherence is a far more useful thing to check than a repeat BMD or a bone turnover marker in a patient on treatment. Check serum calcium (corrected for albumin) before and periodically during denosumab or zoledronic acid therapy, particularly in renal impairment or known vitamin D deficiency. Routine biochemical bone turnover markers are not recommended for routine monitoring — reserve them for the occasional case where adherence or response is genuinely uncertain and other methods have not resolved the question. A new fracture on adherent therapy is not automatically treatment failure — even effective therapy does not prevent every fracture — but it should trigger the Treatment failure pathway below rather than being dismissed.
Common Errors to Avoid
- Stopping denosumab without a planned bisphosphonate transition — this causes rapid bone loss and a real risk of multiple rebound vertebral fractures, not just a return to pre-treatment risk.
- Not teaching the upright/empty-stomach/30-minute rule for oral bisphosphonates in enough detail — poor technique both reduces absorption and raises esophageal injury risk.
- Assuming a normal or osteopenic T-score rules out a treatment need in a patient who has already had a hip or vertebral fragility fracture — fracture history alone can mandate treatment regardless of BMD.
- Starting or continuing romosozumab in a patient with a myocardial infarction or stroke in the past year.
- Ordering bone turnover markers to diagnose osteoporosis or for routine monitoring — they are not validated for either purpose.
- Recommending high-dose calcium or vitamin D supplementation for extra protection beyond the target intake — supra-target vitamin D dosing has no added skeletal benefit and a possible harm signal, and supplementing calcium a patient is already getting from diet only adds GI side effects and stone risk without benefit.
- Skipping dental assessment and counselling before starting long-term bisphosphonate or denosumab therapy in a patient with upcoming invasive dental work.
- Continuing bisphosphonate therapy indefinitely without ever revisiting a drug holiday, or conversely stopping a high-risk patient's bisphosphonate (prior hip or vertebral fracture) purely because 5 years have passed.
- Treating an anabolic agent (teriparatide or romosozumab) as a stand-alone course — bone density gains are rapidly lost unless an antiresorptive agent follows.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
Bisphosphonates
The mainstay of osteoporosis pharmacotherapy — oral alendronate and risedronate, and IV zoledronic acid, are all first-line options. Etidronate, once used cyclically, is no longer marketed in Canada. Strict adherence to the administration instructions is essential for oral agents, since poor technique both reduces absorption and increases esophageal injury risk.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Alendronate | Prevention: 5 mg PO once daily Treatment: 10 mg PO once daily, or 70 mg PO once weekly Glucocorticoid-induced osteoporosis: 5 mg PO once daily (10 mg once daily in postmenopausal women not also taking estrogen) | GI upset, altered taste, esophageal irritation; rare atypical femoral fracture, osteonecrosis of the jaw, acute-phase reaction, ocular inflammation | Contraindicated at a creatinine clearance below 35 mL/min.[2] |
| Risedronate | Prevention: 5 mg PO once daily, or 35 mg PO once weekly Treatment: 5 mg PO once daily, 35 mg PO once weekly (immediate-release or DR), or 150 mg PO once monthly Men, to improve BMD: 35 mg PO once weekly Glucocorticoid-induced osteoporosis: 5 mg PO once daily Paget disease of bone: 30 mg PO once daily for 2 months | GI upset, altered taste, esophageal irritation; rare atypical femoral fracture, osteonecrosis of the jaw, acute-phase reaction, ocular inflammation | Not recommended at a creatinine clearance below 30 mL/min. The delayed-release (DR) tablet is taken with breakfast rather than on an empty stomach. |
| Zoledronic acid | Osteoporosis treatment / BMD in men / glucocorticoid-induced osteoporosis: 5 mg IV once yearly Prevention (osteopenia): A single 5 mg IV infusion Paget disease of bone: A single 5 mg IV infusion; retreatment after 1 year or longer if relapse occurs | Acute-phase (flu-like) reaction in about 1 in 4 patients after the first infusion; rare renal impairment, atrial fibrillation, cerebrovascular event, atypical femoral fracture, osteonecrosis of the jaw | Contraindicated at a creatinine clearance below 35 mL/min. Ensure adequate hydration before and after each infusion. Never give as a bolus injection; infuse over at least 15 minutes. |
| Alendronate / vitamin D3 | Dosing: Alendronate 70 mg with vitamin D3 2800 or 5600 units, once weekly | Same as alendronate, plus those of the vitamin D component at high doses (hypercalcemia, hypercalciuria) | A combination product for a patient who needs both agents and prefers a single weekly tablet. |
RANK Ligand Inhibitor
Denosumab is a first-line option, particularly when a bisphosphonate is contraindicated, not tolerated, or genuinely difficult to take as directed. Unlike a bisphosphonate, denosumab is not retained in bone — stopping it without a transition plan causes a rapid rebound in bone turnover and a real risk of multiple vertebral fractures, so long-term uninterrupted dosing is the expectation, not an option to be revisited casually.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Denosumab | Dosing: 60 mg SC once every 6 months, never delayed more than 1 month | Hypocalcemia (especially with renal impairment or vitamin D deficiency), eczema, serious infection; rare atypical femoral fracture, osteonecrosis of the jaw | Not renally cleared, so no dose adjustment is needed for renal impairment, but hypocalcemia risk is higher in this group — correct vitamin D deficiency and hypocalcemia before the first dose.[4] |
Osteoanabolic Agents
Reserved for a patient at very high fracture risk — a recent severe vertebral fracture, or more than 1 vertebral fracture with a T-score below -2.5 — since bone density gains are rapidly lost after the course ends unless an antiresorptive agent (bisphosphonate or denosumab) follows immediately. Abaloparatide, a related parathyroid hormone-related peptide analogue, is not currently marketed in Canada.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Teriparatide | Dosing: 20 mcg SC once daily | Nausea, dizziness, leg cramps, transient hypercalcemia, orthostatic hypotension immediately after injection | Maximum 24 months of lifetime exposure. Give the injection with the patient sitting or supine because of orthostatic hypotension risk. Follow with an antiresorptive agent. |
| Romosozumab | Dosing: 210 mg SC (two 105 mg injections) once monthly for 12 months | Arthralgia, headache, injection-site reactions; rare serious cardiovascular or cerebrovascular events | Contraindicated within the past year of myocardial infarction or stroke.[6] |
Selective Estrogen Receptor Modulators
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Raloxifene | Dosing: 60 mg PO once daily | Hot flashes, leg cramps; venous thromboembolism risk similar to estrogen | No demonstrated benefit for nonvertebral or hip fracture prevention — reserve for a patient at lower hip-fracture risk. Do not start until menopause is established. |
| Conjugated estrogens / bazedoxifene | Dosing: 1 tablet daily (bazedoxifene 20 mg / conjugated estrogens 0.45 mg) | Breakthrough bleeding/spotting, abdominal pain, muscle spasms, vulvovaginal mycotic infection; increased risk of venous thromboembolism, cardiovascular disease, and breast cancer | Not indicated by Health Canada specifically for osteoporosis prevention — considered only for a patient under 75 with moderate-to-severe vasomotor symptoms and an intact uterus who also wants that benefit. Do not crush or chew. |
Menopausal Hormone Therapy
An alternative rather than a first-choice osteoporosis agent — most appropriate for a postmenopausal female under 60 or within 10 years of menopause who also wants treatment for vasomotor symptoms.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Conjugated estrogens | Dosing: Per current menopausal hormone therapy dosing guidance | Venous thromboembolism, breast cancer risk with long-term combined use, breast tenderness, nausea | Requires a progestin (e.g., medroxyprogesterone acetate) in a patient with an intact uterus, to protect the endometrium. |
| Medroxyprogesterone acetate | Dosing: Per current menopausal hormone therapy dosing guidance | Bloating, mood changes, breakthrough bleeding | Added to estrogen therapy specifically to protect the endometrium in a patient with an intact uterus — not used alone for osteoporosis. |
Calcitonin
A second-line, weaker option. Nasal spray calcitonin has been withdrawn from the Canadian market over a cancer-risk signal identified on regulatory review, leaving only the injectable formulation, mainly used short-term for the pain of an acute vertebral fracture rather than for fracture prevention.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Calcitonin (salmon) | Dosing: Per current product-specific dosing guidance | Nausea, flushing, injection-site reaction; rare hypersensitivity | Off-label, short-term use for acute vertebral-fracture pain; the dose is not standardized. Not used as primary fracture-prevention therapy. |
Nutritional Supplements (foundation therapy for every patient)
Meet the calcium and vitamin D targets through diet first, then supplement only the shortfall.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Calcium carbonate | Females over 50: Total intake (diet + supplement) 1200 mg/day Males 50-70: Total intake (diet + supplement) 1000 mg/day Males over 70: Total intake (diet + supplement) 1200 mg/day | Constipation, bloating; high supplemental doses have been linked to renal stones | Requires an acidic environment for absorption — take with or after meals. May reduce absorption of bisphosphonates, ciprofloxacin, iron, and levothyroxine — separate dosing by at least 2 hours. |
| Vitamin D3 (cholecalciferol) | Adults 50-70: Total intake (diet + supplement) 600 IU/day Adults over 70: Total intake (diet + supplement) 800 IU/day | Uncommon at recommended doses; chronic high-dose use has been linked to hypercalcemia, hypercalciuria, and increased bone loss | Vitamin D3 is preferred over vitamin D2 (ergocalciferol). A minimum 400 IU supplement is advised for all adults 50 and older, in addition to dietary sources.[1] |
References
- Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update — Osteoporosis Canada / CMAJ (Morin SN, Feldman S, Funnell L, et al.). CMAJ 2023;195(39):E1333-E1348
- Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research — Journal of Bone and Mineral Research (Shane E, Burr D, Abrahamsen B, et al.). J Bone Miner Res 2014;29(1):1-23
- FRAX and the assessment of fracture probability in men and women from the UK — Osteoporosis International (Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E). Osteoporos Int 2008;19(4):385-397
- Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension — Journal of Bone and Mineral Research (Cummings SR, Ferrari S, Eastell R, et al.). J Bone Miner Res 2018;33(2):190-198
- 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis — Arthritis & Rheumatology, American College of Rheumatology (Humphrey MB, Russell L, Danila MI, et al.). Arthritis Rheumatol 2023;75(12):2088-2102
- Romosozumab or alendronate for fracture prevention in women with osteoporosis — New England Journal of Medicine (Saag KG, Petersen J, Brandi ML, et al.). N Engl J Med 2017;377(15):1417-1427
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.