Osteoporosis Flashcards
Define osteoporosis.
Osteoporosis is a complex metabolic bone disease characterised by low bone density and micro-architectural defects in bone tissue, resulting in increased bone fragility and susceptibility to fracture
Normal ageing process with normal ratios and normal ALP.
What score defines osteoporosis?
T score of equal to or less than -2.5 = osteoporosis i.e. BMD result is equal to, or more then, 2.5 SDs below the young adult mean BMD
T score -1 to -2.5 = osteopenia i.e. The BMD result is between 1 and 2.5 SDs bellow the young adult mean BMD
What does DEXA stand for?
Dual X ray absorptiometry
?hip and lumbar spine
Define T score on DEXA.
SD from the mean of a young healthy population (useful to determine risk of #)
Define Z score on DEXA.
SD from mean of AGE-MATCHED control (useful to identify accelerated bone loss in younger patients)
What does DEXA stand for?
Dual X ray absorptiometry
?hip and lumbar spine
How does T score correlate with fracture risk?
For each standard deviation fall in BMD, there is an 1.5-3 fold increase risk of fracture
How does osteoporosis usually present?
Asymptomatic until fracture occurs - e.g. NOF, Colle’s.
Fall prevention is first-line therapy.
When is the Z score used?
Children, adolescents, young adults and adults before 50s
T score cannot be used in this population
Which bone is most important for DXA scanning in hyperparathyroidism?
Forearm
A 56 year old woman sustains a right wrist fracture after a fall. She has a T scores of -2.9 at the neck of femur. Which treatment is most appropriate?
Alendronic acid 70mgs once a week and vitamin D3 1000 units once a day - low threshold for post-menopausal women
A 68 year old woman has taken denosumab 60mgs every six months for five years. Her BMD has improved. You decide to stop treatment in order to reduce risks of longer term treatment. How should you advise your patient?
Start and continue alendronic acid or zoledronic acid afor 2 years after treatment
NB: Stopping denosumab can be associated with a ‘rebound’ increase in bone turnover, leading to rapid falls in bone density and vertebral fractures.
What type of bone is most bone made up of?
Cortical 90%
Trabecular 10%
What are the most common sites for osteoporotic fractures?
- Spine
- Neck of femur
- Forearm (Colle’s)
What are the 4 stages of normal bone remodelling?
- Resorption
- Reversal
- Formation
- Resting
What are the risk factors for osteoporosis?
Constitutional
- Female gender
- Age
- Asian or Caucasian
- Sex hormone deficiency
- Previous fragility fracture
- Family h/o fragility fracture
- Comorbidities
- Neuromuscular disorders
Lifestyle
- Low BMI
- Smoking
- Excessive alcohol
- Prolong immobilisation
- Low dietary calcium intake
- Vit D deficiency
List 5 modifiable risk factors for fracture.
- Low BMD
- Steroid use
- Low BMI
- Hypogonadism in men
- Smoking
- Excessive alcohol intake
- Poor diet/low Ca intake
- Vit D deficiency
- Long term immobilisation
What investigations would you do for osteoporosis?
DXA scan (dual-energy x-ray absorptiometry) - DIAGNOSTIC, much less radiation than CXR so safe.
- T score <-2.5 = osteoporosis
- T score <-2.5 with fragility fracture = severe osteoporosis
- T score -1 to -2.5 = osteopenia
X-ray - may show osteopenia and or fractures but is NOT DIAGNOSTIC.
Bloods to rule out cause:
- 25-hydroxyvitamin D levels of <20 nanograms/mL
- Testosterone deficiency
- TFTs - ?hyperthyroidism
- PTH - ?hyperparathyroidism
- Urinary free cortisol - high in Cushing’s
- Serum/urine protein electrophoresis - abnormal in myeloma
- Combination of low serum 25-hVitD, low serum/urine Ca, low serum phosphate and high PTH and AlkPhos = Vitamin D deficiency with or without osteomalacia.
How is osteoporosis managed?
Conservative:
- Weight bearing exercise
- Stop smoking
- Reduce EtOH
- Exclude secondary causes e.g. mets, MM, osteomalacia, Paget’s, endocrine (menopause, hyperthyroid)
Medical -
ALL PATIENTS ON CALCUM + COLECALCIFEROL
1st line: Bisphosphonates e.g. alendronate/risedronate PO - bone resorption reduced (morning on empty stomach). NB: check renal function, CI if eGFR <30ml/min → refer. Continue for 5yrs if well tolerated.
Other:
- Teriparatide SC (PTH derivative) - anabolic
- Raloxifene PO - SERM, used in post-menopausal women if alendronate CI
- Denosumab SC = for prevention and treatment; denosumab is a human monoclonal antibody to RANKL, a cytokine that is involved in mediating osteoclast activity.
- Strontium PO- anabolic + anti-resorptive
What is the recommended calcium and vitamin D3 dose daily?
calcium - 800-1000mgs daily
vitamin D3 - 1000 units daily
Which treatment is used where spinal T scores are very low?
Teriparatide = a peptide including the 34 amino acids of the N terminal part of parathyroid hormone. It is self-injected daily and is expensive so not first line.
What is the most effective intervention for osteporosis in anorexia nervosa?
Weight gain and resumption of periods is better than any other intervention (e.g. COCP, alendronic acid, calcium, vit D3)
What drugs for osteoporosis are contraindicated in very low eGFR?
- Alendronic acid
- Ibandronic acid
- Risedronate
- Zolendronic acid
These are all cleared via the kidneys. Denosumab is a monoclonal antibody and so could be used in the situation
What is important to check before calculating a FRAX score for a patient?
That the correct country has been selected - calculations vary by country
What are the conservative measures for management of osteoporosis?
- Physical activity
- Prevention of falls
- Protein intake
- Fracture Liaison Service ( clinical pathways in liaison with Orthopaedic Units for diagnosis and treatment of osteoporosis in patient with fragility fractures
- Calcium and Vit D supplementation
What are the categories of pharmacological treatment for osteoporosis?
Anti-resorptive
Anabolic
- Parathyroid hormone
- Romosozumab
Which anti-resorptive treatments are used for osteoporosis?
Bisphosphonates, oral or IV - oral 5-10yrs, IV for 3yrs.
- Oral: Alendronic acid, Etidronate, Risedronate, Ibandronate
- IV: Zoledronic acid, Ibandronate
Denosumab, s/c
HRT
Selective oestrogen receptor modulators (SERMs) -Raloxifene
Strontium Ranelate
What is the MOA of Denosumab?
Denosumab= fully human monoclonal antibody (IgG2) to RANKL
RANKL = receptor activator of nuclear factor Kbeta ligand
Which anabolic treatments are used for osteoporosis?
- Parathyroid hormone
- Romosozumab
What is the MOA of romosozumab?
mAb taregtting sclerostin which is a negative regulator of bone formation produced by osteocytes
What is the MOA of bisphosphonates?
Synesthetic analogues of pyrophosphate that bind to hydroxyapatite at site of active bone remodelling
Name 2 contraindications to bisphosphonate use.
- Women of child bearing age
- Breastfeeding
Oral bisphosphonates should not be used in:
- Delayed gastric emptying (i.e. stricture or achalasia)
- eGFR <30
List 5 side effects of bisphosphonates.
- IV: Flu like symptoms (acute phase reaction within 48-72 hrs of treatment
- Upper GI discomfort ( oral); rarely Oesophageal CA
- Muscle & bony pain
- Osteonecrosis of the jaw
- Atypical fragility fracture of the femur
- Other : AF, renal toxicity
What are the side effects of SERMs vs HRT for osteoporosis treatment?
HRT
- increased risk of breast CA,
- stroke
- venous thromboembolism (VTE)
SERMs
- aggravating menopausal symptoms
- stroke
- venous thromboembolism (VTE)
Which bisphosphonate is first line after hip fracture?
Zolendronic acid
What is the MOA of SERMs?
SERMs = non-steroidal , partial agonist that act preferentially as agonist in bone but as antagonist in reproductive tissues
What is the pathophysiology of osteoporosis?
Bone is constantly remodelling.
Osteocytes transmit signals to osteoclasts and osteoblasts which initiates bone remodelling.
Osteoclasts resorb bone matrix by creating resorption pit and then they apoptose sending a signal to osteoblasts to synthesise bone matrix which undergoes minerlisation.
Many factors are involed in regulating bone remodelling e.g. PTH, interleukins, vit D, calcitonin, oestrogen, RANK and RANKL, OPG (osteoprotegerin)
RANKL is expressed by osteoblasts which interact with RANK receptors on osteoclasts. Stimulation of RANK causes osteoclastic formation, function and differentiation. OPG released by osteoblasts naturally inhibitrs RANKL-induced activation of RANK.
Why are postmenopausal women at higher risk of osteoporosis?
In oestrogen deficiency, overexpression of RANKL activity overrides the natural inhibitory activity of OPG.
There is dysregulation in the bone remodelling process.
What are the signs and symptoms of osteoporosis?
Asymptomatic until fracture occurs
Low impact fragility fracture. These may indicate or predispose to fracture:
- Back pain
- Kyphosis
- Impaired vision
- Impaired gait, imbalance, lower-extremity weakness
- Vertebral tenderness
Why might bisphosphonates be given for bony metastases?
- They have good pain relieving properties in most patients
- They reduce bone turnover
- They decrease progression of bony metastases
What are bisphosphonates analogues of?
Bisphosphonates are analogues of pyrophosphate - which usually inhibit mineralisation of bone so they reduce resorption of bone in dose dependant manner by inhibiting recruitement and promiting apoptosis of osteoclasts. They are also incorporated into the bony matrix, and thus may be released by osteoclasts when they resorb bone.
What is shown here?
X ray of lateral thoracic spine
This shows a wedge fracture of T vertebral body - bones are osteopenic, there is kyphosis and a crush fractue in the lower thoracic spine
Osteoporosis is the most common cause of vertebral wedge fracture
