Osteoporosis_Presentation for final.pptx

Diagnosis treatment and recen advances

1. OSTEOPOROSIS – DIAGNOSIS , TREATMENT AND RECENT ADVANCES Moderator – Dr Satish Shervegar Presenter – Dr Sachin Patil

2. Osteoporosis : impact and overview Osteoporosis is a disease characterized by low bone density, deterioration of bone tissue, disrupted bone microarchitecture, compromised bone strength and fracture. According to the World Health Organization (WHO) diagnostic classification, osteoporosis is defined by BMD at the hip or lumbar spine that is less than or equal to 2.5 standard deviations below the mean BMD of a young adult reference population (T-score).

3. Osteoporosis is a risk factor for fracture, just as hypertension is for stroke and hypercholesterolemias for heart disease. While risk is highest in individuals with extremely low BMD, the majority of fractures occur in patients with T-scores better than − 2.5. Non-BMD factors contribute to fracture risk, such as falls, frailty and poor bone quality.

4. SCREENING Women ≥65 and younger women with risk factors (e.g., early menopause, steroid use) should get DXA scans Men ≥70 or younger if risk parallels that of a 70-year-old male

5. Biochemical Markers

6. DIAGNOSIS Clinical Assessment & History - Investigate risk factors: age, sex, family history, prior fragility fractures, corticosteroid use, smoking, alcohol intake, endocrine disorders, low BMI. Bone Mineral Density (BMD) via DEXA -Gold standard at lumbar spine and femoral neck. -T-score thresholds: ≥ −1 (normal), −1 to −2.5 (osteopenia), <_2.5 (osteoporosis).

7. Single Photon absorptiometry- Involves passing a high energy photon from a radioactive source through a peripheral bone such as radius or calcaneus. Bone density was estimated based on degree of attenuation of the beam

8. DEXA DEXA (Dual-energy X-ray Absorptiometry) measures bone mineral density (BMD). Approved by FDA in 1988; gold standard for osteoporosis diagnosis. Uses two energy levels for cortical and soft tissue assessment. Produces T-scores and Z-scores comparing to reference populations.

9. Anatomy & Scanning Sites Common sites: Lumbar spine, hip, forearm, whole body. Lumbar: L1 to L4; Hip: neck, trochanters, intertrochanteric region. Forearm: mid to distal radius and ulna. Site selection based on fracture risk and clinical indication.

10. INTERPRETATION OF DEXA Results from the DEXA are given through a scoring system called the T-score in which the results are compared to the bone mineral density of a healthy young adult. T-score levels include . Normal:  T-score between +1 and -1 Low bone mass:  T-score between -1 to -2.5 Osteoporosis:  T-score of -2.5 or lower Severe osteoporosis:  T-score of -2.5 or lower with one or more fractures

11. SINGH INDEX The trabecular pattern of the proximal end of the femur is an excellent indicator of the severity of the osteoporosis

12. Genant Semiquantitative Criteria

13. Laboratory Evaluation - Serum calcium, phosphate, 25(OH)D, PTH, serum alkaline phosphate, thyroid/liver/renal function, 24-hour urinary calcium to detect secondary causes. Fracture Risk Calculation FRAX tool integrates clinical risk factors ± BMD to estimate 10-year fracture risk Imaging Innovation REMS: a radiation-free ultrasound method correlating with DXA , 91% sensitivity/specificity.

14. • FRAX introduced in 2008 to estimate 10-year fracture probability. • Developed by WHO Collaborating Centre in Sheffield • Focuses on major osteoporotic and hip fractures. • Guides decisions on bone mineral density (BMD) testing and treatment. Introduction to FRAX

15. Limitations of BMD-Based Diagnosis • Osteoporosis traditionally defined by T-score < −2.5. • 60–70% of fractures occur without BMD-defined osteoporosis. • Low sensitivity despite high specificity. • Fracture risk also depends on age, history, and location . Considers competing risk of mortality.

16. REMS (Radiofrequency Echographic Multispectrometry ): a non-ionizing technology for  osteoporosis  diagnosis and for  fracture  risk assessment. REMS processes the raw, unfiltered B- mode ultrasound  signals acquired during an  echo graphic  scan of the axial sites,  femur  and  spine . REMS Technology and Fragility Score: - Bone density alone doesn’t fully predict fracture risk. The Fragility Score is a new measure that looks at bone structure using ultrasound, without relying on BMD. It compares signals from the bone to known patterns from people with and without fractures. Scored from 0 to 100, it has been shown in studies to be as accurate as DXA scans .

17. https://en.wikipedia.org/wiki/Radiofrequency_Echographic_Multi_Spectrometry?utm_

18. MANAGEMENT 1.Non Pharmacological Treatment. - Nutrition - Life style modification - Prevention of fall - Hip protectors 2.Basic therapeutic measures - Ca and Vit D supplementation - Oestrogen and HRT

19. Non-Pharmacologic Treatment Diet changes- A well balanced diet with adequate calcium and vitamin D is essential for healthy bone. Calcium contributor - Dairy products like milk, yogurt, cheese, ice cream, cottage cheese, and fortified orange juice or soy products. Most vitamin D comes from sun induced skin conversion Vitamin D contributors - fatty fish, few unfortified foods.

20. LIFESTYLE MODIFICATIONS Physical activity  weight bearing and muscle strengthening exercises. Exercise improves bone strength by 30%to 50%. Exercise should be life long. Cessation of smoking, alcohol, high caffeine intake. Adequate sun exposure

21. Prevention of falls Exercises like balance training, lower limb strengthening exercises Correction of sensory impairment like correction of low vision and hearing impairments Hip protectors- Prevent direct impact on hip

22. PHARMACOLOGICAL TREATMENT Bisphosphonates (Alendronate, Risedronate, Ibandronate, Zoledronic Acid/ Reclast ) Mechanism: Inhibit osteoclast-mediated bone resorption by binding hydroxyapatite and inducing osteoclast apoptosis. Indications: First-line for most patients; high-quality evidence for reducing vertebral, hip, and non-vertebral fractures. Dosing: Alendronate: 70 mg weekly PO Ibandronate: 150 mg monthly PO or 3 mg IV every 3 months Zoledronic Acid: 5 mg IV once yearly .

23. Efficacy : Broad-spectrum antifracture benefit; zoledronic acid reduces risk of hip/vertebral fractures. Side Effects : Esophageal irritation (oral forms), musculoskeletal pain IV forms: acute-phase flu-like reaction; renal toxicity with zoledronate Rare: osteonecrosis of the jaw (ONJ), atypical femoral fractures (AFF) Duration : Oral – up to 10 years; IV – 3–6 years. Consider drug holiday unless very high risk

24. DENOSUMAB Mechanism: Fully human monoclonal antibody against RANKL → reduces osteoclast activation. Indications: High-risk patients, especially those intolerant to oral bisphosphonates, glucocorticoid-induced osteoporosis, men on ADT, women on aromatase inhibitors. Dosing: 60 mg SC every six months Adverse Events :Infections , dermatologic reactions; rare ONJ and AFF. C/I : Preexisting Hyopcalcemia,Pregnancy,Immunocompromised Take home message : Do not take drug holidays it can cause rebound bone loss and vertebral fractures If stopped, transition to bisphosphonate is essential .

25. Selective Estrogen Receptor Modulators (SERMs): Raloxifene Mechanism: Estrogen agonist in bone; antagonist in breast and uterus. Indications: Postmenopausal women with osteoporosis or high breast cancer risk. Dosing: 60 mg orally per day. Efficacy: Reduces vertebral fracture risk; less effective for hip fractures. Side Effects: Hot flashes, leg cramps, VTE risk, possible stroke

26. Anabolic Agents a) Teriparatide Mechanism : Recombinant PTH (1-34), stimulates osteoblast activity and bone formation. Indications : Severe osteoporosis in men and women, including glucocorticoid-induced. Dosing : 20 µg SC daily for max 24 months. Side Effects : Hypercalcemia, leg cramps, dizziness, rare osteosarcoma risk. C/I : CKD patients b) Abaloparatide Mechanism : PTHrP analog —potent anabolic with less resorption. Indications : Postmenopausal osteoporosis at high fracture risk. Dosing : 80 µg SC daily, up to 24 months.

27. Side Effects : Hypercalciuria, dizziness, nausea; avoid in osteosarcoma risk. Post-Treatment : Switch to antiresorptive therapy. c) Romosozumab Mechanism : Monoclonal antibody to sclerostin; dual anabolic and antiresorptive action via Wnt pathway. Indications : High/very high-risk postmenopausal women; not recommended in those with recent CVD events. Dosing : 210 mg SC monthly for 12 months Side Effects : Headache, arthralgia, injection site reactions boxed warning for MI/stroke.

28. NEWER DRUG Strontium Ranelate Mechanism : Promotes osteoblast activity, inhibits osteoclasts; dual in nature. Side Effects : cardiac rhythm abnormalities ; interactions with calcium/antibiotics. Not in use yet in india .

29. INDICATION FOR SURGERY IN OSTEOPROSIS Fragility fractures not amenable to conservative treatment : Vertebral compression fractures (VCF) Proximal femur fractures (hip) Distal radius, proximal humerus, and pelvic fragility fractures Failed conservative treatment with persistent pain or deformity Spinal instability or neurological deficits in vertebral fractures. Periprosthetic or implant-related fractures in osteoporotic bone

30. RECENT ADVANCES Sclerostin Inhibition – Romosozumab Mechanism : A monoclonal antibody blocking sclerostin, thereby activating Wnt / β- catenin signaling to enhance osteoblast-driven bone formation and reduce resorption Efficacy : In Phase III trials (FRAME, ARCH), monthly 210 mg dosing achieved ~11% ↑ lumbar BMD and reduced vertebral fractures by ~73% (vs placebo) and ~48% (vs alendronate); nonvertebral fractures fell by ~36% Safety : Well-tolerated (headache, arthralgia injection-site reactions), but ARCH trial noted a ~30% increase in myocardial infarction vs alendronate—a key consideration

31. Whole-Body Vibration Therapy & Osteoboost Device Approach : Low-magnitude, high-frequency vibrations stimulate osteogenesis through mechano transduction pathways. Challenges : No standardized protocols yet; deemed promising as adjunctive therapy https://journals.lww.com/md-journal/fulltext/2025/02140/evolving_strategies_for_osteoporosis_management_in.2.aspx?utm_

32. Gut–Bone Axis Therapeutics – Probiotics & Postbiotics Probiotics/Prebiotics : Strains like Lactobacillus and Bifidobacterium modulate inflammation and calcium absorption via SCFAs, showing bone-density benefits in humans and animals. Postbiotic Nanoparticles : Colon-targeted butyric-acid–releasing nanoparticles in rodent models suppressed inflammation and improved bone microarchitecture frontiersin.org+2frontiersin.org+2frontiersin.org+2

33. Senolytics , Autophagy Modulators & Cellular Targets Targets : Approaches address cellular senescence, iron balance, autophagy, and mitochondrial health (e.g., via alpha-ketoglutarate, hydrogen sulfide donors) as emerging therapies miRNA/siRNA Therapies : Nanoparticle-delivered gene modulators targeting miRNAs that regulate osteoblast/osteoclast differentiation show promising epigenetic control in preclinical models pubmed.ncbi.nlm.nih.gov .

34. Thank you