Osteoporosis

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]

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.

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.

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.

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.

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.

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.

• 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.

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]

• 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.

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]

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.

1. Confirm true adherence, including correct administration technique for an oral bisphosphonate (empty stomach, plain water, staying upright), before concluding the drug itself has failed.
2. Confirm and correct calcium and vitamin D adequacy; recheck 25-hydroxyvitamin D if deficiency was previously identified.
3. Screen, or re-screen, for a secondary cause that has not yet been addressed — repeat calcium, alkaline phosphatase, creatinine, TSH, and consider serum protein electrophoresis if not already done.
4. If BMD continues to decline, or a new fragility fracture occurs, despite confirmed adherence and adequate calcium/vitamin D, switch therapy: from an oral bisphosphonate to IV zoledronic acid or denosumab, or to an osteoanabolic agent (teriparatide or romosozumab) if the patient now meets the severe/very-high-risk criteria.
5. Refer to an osteoporosis specialist or endocrinology for genuinely refractory disease, for consideration of combination or sequential anabolic-to-antiresorptive therapy, or whenever the diagnosis itself is in doubt.

• 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.

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.

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.

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.

Selective Estrogen Receptor Modulators

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.

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.

Nutritional Supplements (foundation therapy for every patient)

Meet the calcium and vitamin D targets through diet first, then supplement only the shortfall.