Osteoporosis Screening and Treatment: A Practical Guide for Internal Medicine

Clinical Practice Update — DXA Screening, FRAX Risk Assessment, Bisphosphonate Selection, Anabolic Therapy, Drug Holidays, and Denosumab Transitions

This is an original clinical education article informed by current guidelines and evidence. See References below for source documents.

MDA-OSTEO-2026·15 min read

Clinical Focus

Screening with DXA and FRAX, treatment thresholds, first-line pharmacotherapy, risk stratification (high vs very high), sequential therapy, bisphosphonate holidays, denosumab discontinuation, calcium and vitamin D

Target Audience

Internists, primary care physicians, endocrinologists, rheumatologists, geriatricians, residents

Setting

Primary care, endocrinology clinic, rheumatology clinic, geriatrics

Source Evidence

•USPSTF 2025 Recommendation Statement — Screening for Osteoporosis to Prevent Fractures (JAMA, 2025)
•AACE/ACE 2020 Clinical Practice Guidelines for Diagnosis and Treatment of Postmenopausal Osteoporosis (Endocrine Practice, 2020)
•Endocrine Society 2019 Guideline — Pharmacological Management of Osteoporosis in Postmenopausal Women (JCEM, 2019)
•ACP 2023 Clinical Guideline — Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass

Key Clinical Takeaways

Osteoporosis screening and treatment practical guide showing DXA thresholds FRAX assessment and pharmacotherapy selection algorithm — Overview of osteoporosis screening, risk stratification, and treatment selection.

1Screen all women ≥65 with DXA; screen postmenopausal women <65 who are at increased risk as determined by a clinical risk assessment tool → Who to Screen
2Treat when: T-score ≤-2.5, or fragility fracture regardless of T-score, or T-score -1.0 to -2.5 with FRAX ≥20% for major osteoporotic fracture or ≥3% for hip fracture → When to Treat
3For most high-risk patients, start with a bisphosphonate (alendronate, risedronate, or zoledronate) or denosumab as first-line therapy → Choosing Treatment
4For very high-risk patients (multiple fractures, T-score ≤-3.0, FRAX >30%/>4.5%), consider anabolic therapy first (teriparatide, abaloparatide, or romosozumab) followed by an antiresorptive → Very High Risk
5Consider a bisphosphonate holiday after 5 years of oral or 6 years of IV zoledronate if fracture risk is no longer high — reassess every 2–4 years during the holiday → Drug Holidays
6Never stop denosumab without transitioning to a bisphosphonate or another antiresorptive — abrupt discontinuation causes rebound bone loss and increased vertebral fracture risk → Denosumab Transitions
7Limit teriparatide and abaloparatide to 2 years, romosozumab to 1 year — always follow anabolic therapy with an antiresorptive to consolidate gains → Sequential Therapy
8Maintain vitamin D ≥30 ng/mL and calcium intake of 1,000–1,200 mg/day (diet plus supplements) as adjuncts to pharmacotherapy → Foundational Measures
9Evaluate all patients for secondary causes of osteoporosis before starting treatment (thyroid disease, vitamin D deficiency, coeliac disease, myeloma, hyperparathyroidism, glucocorticoid use) → Initial Evaluation
10Monitor DXA every 1–3 years on treatment; two or more fragility fractures on therapy suggests treatment failure → Monitoring

Who Should Be Screened and When Should You Treat?

The USPSTF (updated 2025) recommends DXA screening for all women aged 65 and older (Grade B), and for postmenopausal women younger than 65 at increased risk as determined by a clinical risk assessment tool such as FRAX (Grade B). Evidence for screening men remains insufficient. The AACE recommends evaluating all women aged 50 and older for osteoporosis risk.

Perform DXA screening of the lumbar spine and hip in all women aged ≥65. For postmenopausal women <65, use a clinical risk assessment tool (FRAX, OST, or ORAI) to identify those at increased risk who should undergo DXA.

Strong RecModerate EvidenceUSPSTF 2025AACE 2020

Initiate pharmacotherapy when any of the following criteria are met: (a) T-score ≤-2.5 at spine, femoral neck, total hip, or 1/3 radius; (b) low-trauma hip or spine fracture regardless of T-score; (c) T-score between -1.0 and -2.5 with a fragility fracture of the proximal humerus, pelvis, or distal forearm; or (d) T-score between -1.0 and -2.5 with FRAX 10-year probability ≥20% for major osteoporotic fracture or ≥3% for hip fracture.

Strong RecModerate EvidenceAACE 2020

Evaluate all patients diagnosed with osteoporosis for secondary causes before starting pharmacotherapy. Minimum workup: CBC, CMP (calcium, renal function, liver function), 25-hydroxyvitamin D, TSH, and serum protein electrophoresis in patients with vertebral fractures. Consider PTH, 24-hour urinary calcium, coeliac serology, and testosterone (in men) based on clinical suspicion.

Strong RecLow EvidenceAACE 2020

Clinical Pearl: A fragility fracture (especially hip or vertebral) diagnoses osteoporosis regardless of T-score. Once osteoporosis is diagnosed, the diagnosis persists even if treatment improves the T-score above -2.5 — do not stop therapy simply because the T-score improves.

Which Treatment Should You Start?

The AACE 2020 guideline stratifies patients into high risk and very high risk. This distinction drives initial drug selection. For high-risk patients, antiresorptive agents are appropriate first-line. For very high-risk patients, anabolic agents should be considered first, followed by transition to an antiresorptive to consolidate bone gains.

Drug Selection by Risk Category: A Practical Guide

Drug	Route / Frequency	Best For	Duration / Holiday	Practical Tips
Alendronate	Oral, weekly (70 mg)	First-line for most high-risk patients	Holiday after 5 years if no longer high risk	Take fasting with plain water; stay upright 30 min. Avoid if eGFR <30–35.
Risedronate	Oral, weekly (35 mg) or monthly (150 mg)	First-line alternative; may have lower GI side effects	Holiday after 5 years if no longer high risk	Same administration rules as alendronate.
Zoledronate	IV, annually (5 mg)	Patients unable to take oral; adherence concerns	Holiday after 6 years (3 annual infusions = minimum)	Acute-phase reaction (flu-like) common after first dose. Ensure adequate hydration. Avoid if eGFR <35.
Denosumab	SC, every 6 months (60 mg)	First-line alternative; safe in CKD; no GI issues	No holiday. Must transition to bisphosphonate if stopping.	Do not delay or skip doses. Rebound vertebral fractures on discontinuation. Check calcium before each dose.
Teriparatide	SC daily (20 mcg)	Very high risk: severe/multiple vertebral fractures	Limit to 2 years. Must follow with antiresorptive.	Anabolic — builds new bone. Orthostatic hypotension early. Gains lost without follow-on antiresorptive.
Romosozumab	SC monthly (210 mg)	Very high risk; dual mechanism (anabolic + antiresorptive)	Limit to 1 year. Must follow with antiresorptive.	Avoid if MI/stroke within past year or high CV risk (boxed warning). Most rapid BMD gains of any agent.

Warning

Stopping denosumab without transitioning to a bisphosphonate causes rapid rebound bone loss and multiple vertebral fractures, sometimes within months. If a patient must discontinue denosumab, prescribe a bisphosphonate (oral or IV zoledronate) to mitigate rebound. Denosumab should not be used if the patient is unlikely to adhere to the every-6-month schedule.

Clinical Decision Pathway

Managing Osteoporosis: 5 Questions

Question 1: Does this patient need screening?

Women ≥65 → DXA screening. Postmenopausal women <65 with risk factors (low BMI, parental hip fracture, glucocorticoids, smoking, excess alcohol, rheumatoid arthritis) → calculate FRAX; if at increased risk, screen with DXA. Men → no universal screening; consider DXA if risk factors or fragility fracture.

Question 2: Does this patient meet treatment criteria?

T-score ≤-2.5, or fragility fracture, or osteopenia with FRAX ≥20% MOF / ≥3% hip → Treat.

Osteopenia with FRAX below thresholds → lifestyle measures, reassess in 2–5 years.

Question 3: Is this patient high risk or very high risk?

Very high risk: recent fracture (past 12 months), multiple vertebral fractures, T-score ≤-3.0, fracture while on antiresorptive, FRAX >30% MOF or >4.5% hip, falls on glucocorticoids → consider anabolic-first strategy.

High risk (not very high) → start bisphosphonate or denosumab.

Question 4: When should you reassess?

DXA every 1–3 years on treatment. After 5 years oral bisphosphonate or 6 years IV zoledronate: reassess risk. If T-score >-2.5 and no recent fractures → consider holiday. If still high risk → continue treatment up to 10 years oral or re-dose IV.

Question 5: What if the patient is on denosumab?

Reassess after 5–10 years. If continuing: keep denosumab on schedule. If stopping: transition to a bisphosphonate to prevent rebound bone loss. Never stop denosumab without a bridge. No drug holiday for denosumab.

Evidence in Context

Where Guidelines Agree

All major guidelines agree on: DXA screening for women ≥65 (and at-risk younger postmenopausal women), the T-score ≤-2.5 treatment threshold, bisphosphonates as appropriate first-line therapy, the need to follow anabolic agents with antiresorptives, the danger of abrupt denosumab discontinuation, vitamin D and calcium as adjuncts, and the need for periodic reassessment of fracture risk during treatment.

Where They Differ

FRAX thresholds: The AACE uses fixed US thresholds (≥20% MOF / ≥3% hip). Some international guidelines use age-dependent thresholds. The AACE 2020 introduced “very high risk” thresholds (FRAX >30% MOF / >4.5% hip) that trigger anabolic-first strategies.

Bisphosphonate holiday timing: The Endocrine Society suggests reassessing at 3–5 years for oral and 6 years for IV. The AACE specifies 5 years oral / 6 years IV. Both agree a holiday is only appropriate if fracture risk has decreased.

Screening in men: The USPSTF finds insufficient evidence. The Endocrine Society and AACE recommend DXA for men ≥70 or those with risk factors.

The Anabolic-First Strategy: What the Evidence Shows

The ARCH trial (romosozumab vs alendronate) and the VERO trial (teriparatide vs risedronate) demonstrated that starting with an anabolic agent followed by an antiresorptive produces greater BMD gains and greater fracture risk reduction than starting with an antiresorptive alone in very high-risk patients. Conversely, starting with an antiresorptive can blunt the subsequent response to an anabolic agent. This has led AACE to recommend an anabolic-first approach for very high-risk patients.

What We Still Don’t Know

Optimal bisphosphonate holiday duration: How long a holiday can safely last and what triggers should prompt restart remain uncertain. Current guidance is largely expert consensus.

Screening and treatment in men: No RCTs have evaluated the effect of screening men on fracture outcomes. Treatment evidence in men is extrapolated largely from postmenopausal women studies.

Best transition strategy from denosumab: While bisphosphonate transition is recommended, the optimal agent, timing, and duration of bridging therapy after denosumab remain under investigation.

References

1.US Preventive Services Task Force. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. 2025;333(6):498–508. doi:10.1001/jama.2024.27154
2.Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis — 2020 Update. Endocr Pract. 2020;26(Suppl 1):1–46. doi:10.4158/GL-2019-0524
3.Eastell R, Rosen CJ, Black DM, et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2019;104(5):1595–1622. doi:10.1210/jc.2019-00221
4.Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, et al. Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians. Ann Intern Med. 2023;178(6):784–799. doi:10.7326/M22-1239

How to Read the Evidence Tags

Every recommendation carries two tags. These are Medaptly’s own simplified interpretations for educational clarity.

Recommendation Strength

Tag	Meaning	In Practice
Strong Rec	Benefits clearly outweigh risks.	Standard practice.
Moderate Rec	Evidence favours benefit.	Most patients should receive this.
Conditional Rec	Right choice depends on individual.	Shared decision-making.
Against	Risks outweigh benefits.	Avoid.

Evidence Quality

Tag	Meaning	Confidence
High Evidence	Multiple RCTs or meta-analyses.	Very confident.
Moderate Evidence	Single RCT or large observational studies.	Reasonably confident.
Low Evidence	Expert consensus or small studies.	May change.

These are Medaptly’s simplified interpretations. Consult original documents in References for full details.

Article Information

For Educational Purposes Only. This is original clinical education content informed by current published guidelines and clinical evidence. It does not constitute medical advice, is not endorsed by AACE, the Endocrine Society, USPSTF, ACP, or any other organisation, and does not replace individualised clinical judgement, institutional protocols, or local formulary guidance. Drug dosages should always be verified against current prescribing information before prescribing. Readers are encouraged to consult the original source guidelines listed in the References section for the full evidence review and complete recommendation sets.