Management of Fracture Risk in Patients with Diabetes—Chinese Expert Consensus (2019)

1. Basic Information

2. Core Mechanisms & Clinical Features

1. Type 2 Diabetes Mellitus (T2DM)
   • Bone impairment: microarchitectural destruction, advanced glycation end-products (AGEs) in bone matrix, reduced bone turnover, decreased bone strength.
   • Fall risk: peripheral neuropathy, retinopathy, poor balance, hypoglycemia, nocturia → 1.5–2.0× higher hip/vertebral fracture risk vs. non-diabetics; BMD often overestimates bone strength.
    
2. Type 1 Diabetes Mellitus (T1DM)
   • Insufficient peak bone mass acquisition, suppressed bone turnover, significantly reduced BMD; fracture risk far higher than T2DM, requiring early screening in adolescence.
    
3. Key Contradiction
   • DXA-measured BMD underestimates T2DM fracture risk (fractures can occur at “normal” BMD) but still has predictive value.
   • FRAX®: replace rheumatoid arthritis (RA) with diabetes to correct risk calculation for diabetic patients.
    

3. Fracture Risk Stratification & Assessment (Mandatory + Recommended)

3.1 Mandatory Assessment (All Diabetic Patients)

• Baseline: DM duration/type, HbA1c, complications (neuro/retino/nephro/peripheral vascular), prior fracture/fall history, family fracture history, lifestyle (smoking/alcohol/exercise/calcium/Vitamin D intake).
• BMD (DXA): PA lumbar spine + femoral neck/total hip + distal 1/3 radius; T-score ≤-2.5 = osteoporosis; -2.5<T<-1.0 = osteopenia; ≥-1.0 = normal (caution: “normal BMD with high fracture risk” in T2DM).
• FRAX®: 10-year hip/major osteoporotic fracture probability; replace RA with diabetes for accuracy.
• Fall risk: Timed Up and Go (TUG), balance test, vision/nerve conduction velocity/orthostatic BP screening.

3.2 Recommended Assessment (High-Risk Patients)

• Bone quality/strength: Vertebral Fracture Assessment (VFA), HR-pQCT, bone turnover markers (BTMs: PINP, β-CTX).
• Secondary causes: PTH, 25(OH)D, renal function, glucocorticoid use, gonadal function (menopause/hypogonadism).

3.3 Risk Stratification

4. Bone Safety of Antidiabetic Agents & Selection

4.1 Preferred (Bone-Safe/Neutral/Beneficial)

• Metformin: Neutral/potentially bone-protective; first-line, preferred if no contraindications.
• GLP-1 RAs: Neutral/potentially bone-protective; ideal for obese/CVD-high patients.
• DPP-4 inhibitors: Neutral; suitable for most patients.
• α-glucosidase inhibitors: Neutral; good for postprandial hyperglycemia.

4.2 Caution/Avoid (Especially High-Risk)

• Thiazolidinediones (TZDs: pioglitazone/rosiglitazone): definitely increase fracture risk, especially postmenopausal women; avoid in high-risk patients.
• SGLT-2 inhibitors: Some studies suggest increased fracture risk (elderly/renal impairment); individualized assessment, avoid in very high-risk.
• Sulfonylureas/insulin: hypoglycemia increases fall risk; optimize dose to avoid severe hypoglycemia (<3.9mmol/L); insulin may cause weight gain, indirect bone impact—control weight.

4.3 Glycemic Targets (Balancing Bone Safety)

• General: HbA1c <7.0%.
• Elderly/frail/high fracture risk: HbA1c 7.0%–8.0%, strictly avoid hypoglycemia to reduce fall triggers.

5. Anti-Osteoporosis Therapy (Initiation Criteria & Regimens)

5.1 Initiation Criteria (Any One)

• History of vertebral/hip fragility fracture;
• DXA T-score ≤-2.5 (lumbar spine/total hip/femoral neck/distal radius);
• Osteopenia (-2.5<T<-1.0) + fragility fracture (humerus/forearm/pelvis);
• FRAX 10-year hip fracture probability ≥3% or major osteoporotic fracture probability ≥20% (diabetes-adjusted).

5.2 Drug Selection & Regimens (Individualized)

5.3 Monitoring & Sequencing

• Monitoring: DXA every 1–2 years; BTMs every 3–6 months; vertebral X-ray/VFA annually; glycemia/renal function/electrolytes regularly.
• Sequencing: Anabolic first (teriparatide), then anti-resorptive (bisphosphonate/denosumab) to avoid bone rebound; bisphosphonate “drug holiday” after 3–5 years (not recommended for high-risk).

6. Fall Prevention (Key for Primary Fracture Prevention)

1. Environmental modification: Remove obstacles, install handrails, non-slip flooring, night lighting, bathroom handrails.
2. Behavioral intervention: Regular exercise (brisk walking, Tai Chi, resistance training, ≥150min/week); balance training (TUG, single-leg stand); non-slip shoes; avoid solo night activity.
3. Medical intervention: Optimize antidiabetics to prevent hypoglycemia; correct vision/hearing; treat peripheral neuropathy/orthostatic hypotension; discontinue dizziness/fall-inducing drugs (benzodiazepines, α-blockers).
4. Assistive devices: Cane/walker if needed; hip protectors (very high-risk).

7. Post-Fracture Comprehensive Management (Secondary Prevention)

7.1 Acute Phase

• Glycemic control: Stress hyperglycemia → insulin pump/IV insulin preferred; target 7.8–10.0mmol/L, avoid hypoglycemia; monitor ketones, electrolytes, renal function.
• Fracture treatment: Early reduction/fixation (surgical/conservative), minimally invasive preferred; prevent infection, VTE, pressure ulcers, pneumonia; nutritional support (high-protein + calcium/Vitamin D + zinc/magnesium).
• Pain management: Multimodal analgesia (NSAIDs + acetaminophen, avoid long-term opioids); calcitonin for acute vertebral fracture pain.

7.2 Recovery & Secondary Prevention

• Early rehabilitation: Bed activity 24–48h post-op, gradual ambulation; physical therapy + functional training to restore strength/balance.
• Intensified anti-osteoporosis: Initiate immediately post-fracture (unless contraindicated); anabolic + basics preferred; avoid TZDs, optimize antidiabetics.
• Refracture prevention: Enhanced fall intervention + long-term anti-osteoporosis + regular follow-up (DXA + vertebral X-ray + FRAX).

8. Follow-Up & Closed-Loop Management

8.1 Follow-Up Frequency

• Low-risk: Annual (DXA + FRAX + fall assessment).
• Intermediate/high-risk: Every 3–6 months (glycemia + BTMs + fall); DXA every 1–2 years; vertebral X-ray/VFA annually.
• Post-fracture: 1, 3, 6, 12 months post-op, then annually.

8.2 Multidisciplinary Team (MDT)

• Endocrinology (glycemia + osteoporosis), Orthopedics (fracture treatment), Rehabilitation (functional training), Geriatrics (fall + comprehensive assessment), Nutrition (nutritional support).

9. Clinical Quick Reference Card (Rapid Implementation)

10. Core Value & Extensions

• Core Value: Corrects the misconception “normal BMD in diabetes = no fracture risk”; establishes a glycemic control – anti-osteoporosis – fall prevention triad to reduce fragility fracture incidence, disability, and mortality.
• Extensions: T1DM requires early bone screening (adolescence); elderly/frail patients need relaxed glycemic targets and bone-safe antidiabetics; special populations (pregnancy, renal impairment, glucocorticoid users) need individualized regimens.