Osteoporosis

Metabolic bone disease, characterized by low bone mass and deterioration of the architecture of bone tissue, which in combination leads to bone fragility and fracture

Under treated, only 10% of men with osteoporosis and 30% post menopausal women with fractures receiving treatment

Classically fracture of low trauma to hip, forearm and spine

Osteoporosis Course

• Peak bone mass occurs at 20-35 years
• Decline in bone mass starts after age 35-50 years
• Normal bone density loss is 1% per year
• Hypogonadism accelerates decline to 3-4% per year
• Menopause in women
• Orchiectomy in men (Prostate Cancer)
• Age 50 years
  • Osteopenia in Men: 33-47%
  • Osteoporosis in Men: 4-6%
• Age 65 years
  • Men and women have similar rates of decline
• Age 75 years
  • Dramatic increase in Incidence of Hip Fracture in men
• Age 80 years
  • Women: 90% have osteoporosis (15% Hip Fracture risk)
  • Men: 50% have Osteoporosis
• Age 90 years
  • Women: Hip Fracture in 33%
  • Men: Hip Fracture in 17%

Osteoporosis Types

  Type 1 Osteoporosis

• observed in postmenopausal women
• Estrogen plays a crucial role in maintaining bone density. After menopause
• –> the decline in estrogen levels –> lead to increased bone resorption (breakdown) without sufficient new bone formation –> decrease in trabecular bone mass and increased susceptibility to fracture
• (Trabecular bone: inner, spongy part of bones, is particularly affected by estrogen deficiency. trabecular bone is more metabolically active and is more vulnerable to rapid changes in bone turnover)
• Fracture sites
  • Vertebral body (T7-T9)
  • Distal forearm (Colles Fracture)

  Type 2 Osteoporosis

• Both sexes, Age over 60 years
• It is characterized by age-related bone loss and a decrease in the overall both cortical and Trabecular Bone mass decreased
• Fracture sites
  • Femoral neck (Most common)
  • Proximal humerus
  • Proximal Tibia
  • Pelvis

Osteoporosis Secondary Causes

Endocrine Causes

•     Hyperparathyroidism
•     Grave’s Disease or Hyperthyroidism
•     Cushing’s Disease
•     Hyperprolactinemia (Prolactinoma)
•     Hypogonadism
•     Women: Menopause

 Miscellaneous Medical Conditions

•     Chronic Renal Failure
•     Malnutrition
•     Rheumatoid Arthritis
•     Chronic Liver Disease
•     Mastocytosis
•     Spinal cord injury
•     Calcium deficiency (e.g. Hypercalciuria)
•     Organ transplant
•     Alcoholism
•     Gastric Bypass Surgery
•     Malabsorption syndromes
•     Vitamin D Deficiency

  Malignancy

•      1. Multiple Myeloma
•      2. Leukemia
•      3. Lymphoma
•      4. Ectopic ACTH Syndrome

 Medications

• Corticosteroids (systemic and inhaled)
• Thiazolidinediones (Rosiglitazone, Pioglitazone)
• Levothyroxine at excess doses (not when TSH normal)
• Agents causing Hypogonadism
  • Aromatase Inhibitors (e.g. Femara or Letrozole)
  • GnRH agonists
  • Parenteral Progesterone (Depo Provera)
• Anticonvulsants (accelerate bone loss in elderly 70%)
  • Increase Vitamin D and sex steroid metabolism
  • Increase renal calcium excretion
• Heparin (prolonged use)
• Methotrexate (at higher doses for longer duration)
• Vitamin A in excess (>10,000 units per day)
• Loop Diuretics
  • (decreased renal calcium absorption)
• Proton Pump Inhibitors
  • (decreased calcium absorption)

Risk Factors

• Age >70yo
• Age males >60 and females >50 plus:
• FHx low trauma fracture
• smoking
• high EtOH intake >2/day
• diet low in calcium
• low body weight
• recurrent falls
• sedentary lifestyle over many years
• Endocrine disorders:
  • Cushing’s syndrome (iatrogenic or due to organic pathology)
  • Hypogonadism and functional hypothalamic amenorrhea
  • Type 1 diabetes mellitus
  • Growth hormone deficiency
  • Hyperthyroidism
  • Hyperparathyroidism
  • Complete androgen insensitivity
  • Subtherapeutic transgender hormone therapy
• Inflammatory conditions:
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Cystic fibrosis
  • Ankylosing spondylitis
• Malabsorption
  • Crohn’s disease
  • Ulcerative colitis
  • Celiac disease
  • Gastric bypass surgery
• Psychiatric disease
  • Schizophrenia
  • Anorexia nervosa
• Organ or bone marrow transplant
• CKD
• CLD
• Long term steroids
• Multiple myeloma
• Drugs: antiepileptics, anti-oestrogen, anti-androgen, excess thyroxin, SSRIs

Osteoporosis Evaluation

• Diagnostic Criteria (in postmenopausal women and men aged >50 years)
  • Fragility/Minimal Trauma Fracture
    1. HIP or VERTEBRAL fracture
       • DXA to establish baseline BMD –recommended but not essential
    2. Minimal trauma fracture at any other site (Excluding fingers and toes)
       • T-score ≤–1.5
         • 🡪 need to start treatment» Bisphosphonates (Grade A), Denosumab (Grade A women, Grade B men), Oestrogen replacement therapy (Grade A)
       • T-score ≤–1.5
         • Consider specialist referral
         • Implement falls reduction strategies (Grade A)
         • Encourage balance training and resistance exercise (Grade A)
         • Modify diet, smoking and alcohol intake (Grade C)
         • Provide education and psychosocial support (Grade D)
    3. Minimal trauma fracture
       • A fracture resulting from a low-level trauma that would not normally result in a fracture in a healthy individual.
       • Examples include fractures occurring from:
         • A fall from standing height or less.
         • A minor bump or collision.
         • Routine activities such as bending, lifting, or coughing.
  • No history of minimal trauma fracture
    • DEXA SCAN- spine and proximal femur (Grade A) -if
      1. Aged ≥70 years – The MBS reimburses costs for measurement of BMD testing in any person aged ≥70 years <OR>
      2. Assess risk factor profile-Major risk factors that qualify for MBS reimbursement of DXA
         • Non-Modifiable Risk Factors
           • Parental history of fracture
         • Modifiable and Lifestyle Risk Factors
           • Premature menopause
           • Hypogonadism
           • Multiple falls
           • Low physical activity or immobility
           • Low body weight
           • Low muscle mass and strength
           • Poor balance
           • Protein or calcium undernutrition
           • Smoking
           • Alcohol consumption (>2 standard drinks/day)
           • Vitamin D insufficiency
         • Diseases or Conditions
           • Rheumatoid arthritis
           • Hyperthyroidism
           • Hyperparathyroidism
           • Chronic kidney disease
           • Chronic liver disease
           • Coeliac disease or malabsorption
           • Diabetes mellitus
           • Myeloma or MGUS (Monoclonal Gammopathy of Undetermined Significance)
           • Organ transplant
           • Bone marrow transplant
           • HIV infection
           • Depression
         • Medications with Large Effect
           • Glucocorticoids (>3 months ≥7.5 mg/day)
           • Excess thyroid hormone replacement
           • Aromatase inhibitors
           • Anti-androgen therapy
         • Medications with Modest Effect
           • SSRIs (Selective Serotonin Reuptake Inhibitors)
           • Anti-psychotics
           • Thiazolidinediones
           • Anti-epileptic medications
           • PPIs (Proton Pump Inhibitors)
      3. T-score ≤–2.5
         • Initiate treatment with anti-osteoporosis medication
           • 🡪 need to start treatment: Bisphosphonates (Grade A), Denosumab (Grade A women, Grade B men), Oestrogen replacement therapy (Grade A)
      4. T-score >–2.5 (ostepenia range) then DO
         • Estimate absolute fracture risk Garvan Fracture Risk Calculator or FRAX Tool
           • FRAX Tool:
             • Calculates 10-year risk for hip or major osteoporotic fracture (hip, clinical spine, humerus, or wrist).
             • takes account of – age, gender, weight, height, previous fractures, family history, smoking, alcohol use, glucocorticoid use, rheumatoid arthritis, and secondary osteoporosis
             • Significant fracture risk:
               • Hip fracture probability >5% 🡪 need to start treatment
               • Major osteoporotic fracture probability >20% 🡪 need to start treatment
             • Limitations:
               • Dichotomised risk factors
               • Only uses femoral neck T-score
               • Age Limitation: Designed primarily for individuals aged 40-90 years, limiting its use outside this age group.
               • Overestimation or Underestimation of Risk: May overestimate risk in some populations (like those with high BMI) and underestimate in others (like those with a recent significant weight loss).
             • Garvan Fracture Risk Calculator:
               • Can be used with or without BMD measurement.
               • Quantifies the number of fractures and includes patient’s history of falls.
               • Provides 5-year and 10-year risk for hip or any fracture.
               • Limitations:
                 • Absence of other clinical risk factors in risk calculation

FRAX Tool  – TOOL (australia)

• DEXA Scan
  • Sites
    • Lumbar Vertebrae
      • Assess risk of Vertebral Compression Fractures
      • Screening younger patients without Osteoarthritis
    • Femoral Neck
      • Assess risk of Hip Fractures
      • Screening older patients with Osteoarthritis
    • Other locations
      • Wrist
      • Calcaneus
      • References
  • Advantages
    • Negligible radiation  (4 microsievert)
    • High precision, reproducible, correlates well with fracture risk
  • Disadvantages
    • Affected by many artefacts, including previous fractures, spinal pathology, extrinsic artefacts, obesity

• Scoring
  • Scores are not interchangeable across imaging types
  • 
  • Scores are based on standard deviations below mean
  • Example: T-Score of -2 is two S.D. below the mean
  • T-Score (WHO standard BMD measure)
    • SDs of the BMD measurement above or below the mean BMD of young healthy adults of the same sex.
    • According to the World Health Organisation, osteopenia and osteoporosis can be diagnosed in individuals over 50 and in menopausal women, based on the T-scores.
    • Fracture risk increases 2-3x per T unit
    • T-Score is best indicator of Fracture risk
    • Example: T-Score of -2 confers Fracture risk 4-6x
    • Z-Score
      • SDs of the BMD above or below the mean BMD of adults of the same age and sex
      • Accounts for age, weight, and ethnicity
      • Fracture risk increases 2x per Z unit
      • Measures Fracture risk for remaining lifespan
      • Example: Z-Score of -2 confers Fracture risk 4x
  • Interpretation: T-Score or Z-Score
    • Normal: <1 Standard Deviation (SD) below the mean
    • Osteopenia: 1.0 to 2.5 SD below the mean
    • Osteoporosis: >2.5 SD below the mean
  • Monitoring: Osteopenia and Osteoporosis
    • Recheck DEXA Scan
    • Normal or only mild Osteopenia of femoral neck: Recheck DEXA in 15 years
    • Moderate Osteopenia: Recheck DEXA in 5 years
    • Severe Osteopenia: Recheck DEXA Scan in 1 year
    • Osteoporosis: Recheck DEXA every 2 years or less

Bloods – Further Investigations

• FBE/CMP/eLFT/Vit D/PTH/ testosterone in males/coeliac serology/urinary/serum immunophoresis/24 hour urinary cortisol
  • evaluating for Osteoporosis Secondary Causes
    • Complete Blood Count : Multiple Myeloma
    • Alkaline Phosphatase increased : Paget’s Disease
    • Hepatic Aminotransferase levels (AST, ALT) increased: Hepatic disease
    • Serum Albumin decreased: Malnutrition
    • Serum Creatinine increased: Renal disease
    • Increased Ionized Serum Calcium:
      • Hyperparathyroidism. Cancer
    • Decreased Calcium:
      • Vitamin D Deficiency. Malabsorption
    • Thyroid Stimulating Hormone (TSH) decreased: Hyperthyroidism
    • Hypogonadism: Men: Total Serum Testosterone – Testicular Failure
    • Women: Estradiol: Consider in pre- or peri-menopausal women
      • Unnecessary in post-menopausal women
  • High risk for secondary cause
    • Hypercalciuria
      • 24 hour Urine Calcium excretion >250 mg
    • Vitamin D Deficiency
      • Serum 1,25-Hydroxy Vitamin D decreased
    • Hyperparathyroidism
      • Intact Parathyroid Hormone (PTH) increased
    • Cushing’s Disease
      • 24 hour Urine Cortisol
    • Multiple Myeloma evaluation
      • Serum Protein Electrophoresis (SPEP)
    • Hemochromatosis
      • Serum Iron increased
      • Ferritin level increased
    • Celiac Sprue
      • Tissue transglutaminase and Endomysial antibodies

Management

Lifestyle  

• **weak evidence of decreased fracture from only lifestyle Mx
• Quit smoking
• Appropriate weight
• Falls prevention
• Adequate weight bearing exercise (skipping, jumping better than swimming, walking, riding)
• Decrease EtOH
• Limit PPI

Vitamin D

• Primarily formed in skin from sunlight exposure.
• Small dietary amounts in oily fish, liver, and eggs.
• Production depends on skin color, location, and time of year.
• Does not effect Bone Mineral Density, Muscle Strength, fall risk or function 
• Mixed evidence on vitamin D supplementation preventing bone loss and fractures
  • Increases bone density 1% per year
• Beneficial for high-risk groups
  • aged care residents
  • housebound people
• No benefit from Vitamin D supplement
  • Postmenopausal women in community
  • age <75
• measurement only recommended for high risk groups
• aim levels >50 before bisphosphonate commencement
• levels > 75 recommended

Calcium

• Meta-analyses show no correlation between dietary calcium intake and fracture risk.
• Best dietary sources:
  • milk, hard cheeses, yoghurt.
• Moderate sources:
  • firm tofu, almonds, sesame seeds, tinned fish, some green leafy vegetables, calcium-enriched soy milk.
• Advise adequate dietary calcium intake:
  • 1300 mg/day for women >50 and men >70 years of age
  • 1000 mg/day for men 50–70 years of age
• Does not increase bone density (but slows loss)
• Overdosage above 1500 mg daily weakens bone
• Mixed evidence on dietary calcium and fracture risk.
• Meta-analyses show no correlation between dietary calcium intake and fracture risk.
• Harm with supplemental calcium; supplements not generally recommended.
• Calcium supplementation may be needed when starting medication if dietary intake is insufficient.

Calcium and vitamin D supplementation are not recommended for routine use in non-institutionalised older people

Bisphosphonates

• decrease rate of bone loss and decrease fracture rates
• Increases bone density 5-6% per year
• Consider stopping oral Bisphosphonates after 5 years (and reclast after 3 years)

Generic name	Route	Dose	Frequency
Alendronate	orally	70mg	Weekly for 5-7 years
Alendronate	orally	10mg	Daily for 5-7 years
Risendronate (actonel)	orally	35mg	Weekly for 5-7 years
Risendronate	orally	150mg	Monthly for 5-7 years
Zoledronic acid	IV	5mg	yearly for 3 years

• Zoledronic acid infusion (Aclasta) criteria
  • Must have Vit D level > 50 nmol/L
  • Serum calcium 2.10-2.60 mmol/L
  • eGFR > 35ml/min/1.73m2  
• SE:
  • Oesophagitis
  • Gastritis
  • nausea
  • dyspepsia
  • Osteonecrosis of jaw is a rare complication
    • Consider patient risk of MRONJ before starting osteoporosis therapy.
    • Ensure high-risk patients receive a dental review prior to therapy initiation.
    • mainly occurs with IV treatments and have had dental surgery
    • Little benefit to cessation prior to dental extraction.

• To minimise upper GI side effects advise patients to take first thing in morning (empty stomach) and remain upright for ≥ 30mins 
• not to be taken with calcium or antacids

• BMD response r/v 2 yearly
  • Oral therapy continued for up to 5 years and iv therapy for 3 years
  • After 5 years of oral bisphosphonates or 3 years of intravenous bisphosphonates, a “drug holiday” can be considered in patients at low-to-moderate fracture risk.
  • Patients at high fracture risk may continue therapy for up to 10 years.
• Keep treatment going if:
  • Femoral neck T-score lower than -2.5 w/o vertebral fractures
  • Femoral neck T-score lower than -2.0 with vertebral fractures
  • A recent fracture has occurred

Raloxifene

• Selective oestrogen receptor modulator (SERM)
• prevents post menopausal bone loss
• not shown to prevent non-vertebral fractures
• increased incidence hot flushes, risk DVT, stroke
• Reduces risk of breast cancer, but increase risk DVT/Stroke
• Raloxifene 60mg orally daily
• PBS streamlined authority –minimal trauma fracture and diagnosis with CT or MRI

HRT

• long term management >5yrs rarely indicated for treatment of OP
• Benefits may not outweigh risks of CVA, VTE, CAD, Breast Cancer
• shown to decrease fracture rates

Strontium

• decreased bone resorption
• decreases fractures
• only registered for female use
• 2g orally daily

Teriparatide

• -synthetic PTH, increases bone formation
• -must be specialist initiated
• -daily 20mcg subcut

Denosumab(Prolia)

• monoclonal antibody inhibits osteoclast activity
• Correct vitamin D prior to initiation as may exacerbate hypocalcemia
• 60mg subcut injection q 6 monthly
• PBS streamlined authority
• Well tolerated by patients
• Stopping denosumab after long-term use can lead to a rebound effect with rapid bone loss and increased risk of vertebral fractures.
  • Evidence suggests a significant increase in fracture risk within 12-24 months after stopping
  • Current guidelines recommend continuing denosumab as long as the patient is at high risk of fracture.Transition to another anti-resorptive therapy (e.g., bisphosphonates) is suggested if denosumab is stopped.
• Assess dental hygiene
  • rarely cx osteonecrosis of jaw
  • Invasive dental procedures should be performed just prior to the next six-monthly injection.
  • The in vivo effect on bone suppression will be waning at this time

Denosumab	Bisphosphonates
pros: – More significant increase in BMD compared to bisphosphonates. – Rapid onset of action and potent antiresorptive effects. – Effective in patients with renal impairment.	pros: – Long-term data on fracture prevention. – Oral and intravenous administration options. – Accumulate in bone, providing a residual effect after stopping.
cons: – Increased risk of hypocalcemia. – Rebound bone loss and increased fracture risk upon discontinuation. – Possible increased risk of serious infections and skin reactions.	cons: – Gastrointestinal side effects (with oral forms) – Risk of osteonecrosis of the jaw and atypical femoral fractures (with long-term use). – Renal toxicity (particularly with intravenous forms)

BMD Review

• -monitor 1-2 yearly while on treatment
• -if high risk monitor 2 yearly
• -check 12 months if significant change in treatment
• -if not improved or decreased secondary causes of OP need to be excluded

Children

• -usually secondary to long term steroid use
• -also caused by malignancy, malabsorption, poor nutrition, anorexia, hypogonadism

Men

• -1/3 >60yo will have OP fracture, of which 60% are due to secondary OP
• -need investigations and endocrinology referral

Considerations

• eGFR <35 bisphosphonates and <30 strontium and teripartide contraindicated
• Steroids fracture risk increased 75% in first 3 months use, BMD should be assessed prior to long term initiation
• -discontinuation: half patients stop taking in 6 months, two thirds by 12 months

Prevention

Activity

• Regular, high-intensity weight-bearing exercise slows bone density loss in postmenopausal women and older men.
  • Effective activities: jogging, dancing, tennis, step aerobics.
  • Strength and resistance training (e.g., weight lifting) recommended.
  • Exercise should be progressive, varied, 30 minutes, 2-3 times per week.
  • Short, intense sessions are better than prolonged, less intense exercise.
  • High-intensity balance training decreases fall and fracture risk.
  • Modify activity recommendations for people with osteoporosis.
  • Avoid high-impact activities for those with established osteoporosis.
  • Supervision by a physiotherapist or trained professional recommended.

Smoking Cessation

• Associated with higher rates of fragility fracture but interventions have not shown to reduce fractures.
• Highly recommended for other health reasons.

Avoid Underweight

• Low body weight may lead to lower muscle and bone mass.
• Exercise and diet are important for maintaining healthy weight and bone density.

Hypogonadism

• Should be managed in its own right.
• Not generally treated pharmacologically just for fracture prevention.

Minimize Steroid Use

• >3 months on oral steroids increases fracture risk.
• High-dose inhaled steroids can impact bone mass in children.

Detect and Manage Malabsorption and Chronic Inflammatory Conditions

• Important for vitamin D and calcium absorption.
• Conditions to consider: inflammatory bowel disease, coeliac disease, surgical short gut, chronic arthritis.

Recurrent Falls

• Multimodal falls prevention interventions have good evidence and may reduce fractures.
  • Exercise Programs:
    • Strength and Resistance Training:
      • Focus on building muscle strength and improving balance.
      • Recommended activities: weight lifting, resistance bands, body-weight exercises.
      • High-intensity balance training can reduce fall risk.
    • Balance and Flexibility Exercises:
      • Tai Chi and yoga to improve balance and flexibility.
      • Activities that challenge balance, such as standing on one leg.
    • Weight-Bearing Activities:
      • Walking, dancing, and low-impact aerobics to improve bone density and overall mobility.
  • Home Hazard Assessment and Modification:
    • Identify and mitigate fall hazards in the home environment.
    • Install grab rails in bathrooms and stairways.
    • Ensure adequate lighting throughout the home.
    • Use non-slip mats and remove loose rugs.
    • Arrange furniture to create clear pathways.
  • Medication Review:
    • Regularly review medications to identify those that may increase fall risk (e.g., sedatives, antihypertensives).
    • Adjust dosages or discontinue unnecessary medications under medical supervision.
  • Vision Correction:
    • Regular eye exams to ensure proper vision.
    • Update eyeglasses prescriptions as needed.
    • Consider wearing single-lens glasses instead of bifocals or multifocals when walking outside.
  • Footwear and Foot Care:
    • Wear supportive, well-fitting shoes with non-slip soles.
    • Address foot problems such as bunions or calluses that can affect balance.
  • Education and Training:
    • Provide education on fall prevention strategies.
    • Encourage awareness of individual risk factors and proactive management.
    • Training in how to get up safely after a fall.
  • Assistive Devices:
    • Use of canes, walkers, or other assistive devices for those with mobility issues.
    • Ensure proper fitting and training in the use of these devices.
  • Community-Based Programs:
    • Participation in local fall prevention programs and classes.
    • Access to resources and support groups for fall prevention.

Adequate Vitamin D

• Expect lower levels at the end of winter.
• Safe sun exposure and supplements are recommended where feasible or adequate.

High Alcohol Intake

• Associated with higher fracture rates similar to smoking.
• Reduction recommended for overall health reasons.

Hip Protectors

• Foam pads (soft) or plastic shields (hard) worn over hips in special underwear.
• Reduce hip fracture risk in older people in aged care facilities.
• Number needed to treat (NNT) for one year to prevent one fracture is 91.
• Not effective in community settings due to low usage.