OSTEOPOROSIS Flashcards
What are the 3 forms of calcium in the blood?
45% Bound to proteins e.g. albumin - not diffusable and not biologically active
40% Free-ionised - this is diffusable and biologically active
15% Bound to anions e.g. phosphate - diffusable but not biologically active
The 3 molecules which regulate the amount of calcium in the blood?
Calcitriol (vit D)
Parathyroid hormone
Calcitonin
Outline how vitamin D is synthesised?
7-dehydrocholesterol is converted into vitamin D3 under the influence of UV radiation.
In the liver, vitamin D3 is converted into 25-hydroxyvitamin-D by 25-hydroxylase. This is relatively inactive.
In the kidney, 1-α-hydroxylase converts 25-hydroxyvitamin-D into 1,25-dihydroxyvitamin-D, otherwise known as calcitriol. This is metabolically active.
Calcitriol is then released into the blood stream
How does vitamin D affect calcium levels?
Calcitriol stimulates intestinal epithelial cells to increase the synthesis of calbindin-D proteins. These proteins increase intestinal absorption of calcium by facilitating the transport of calcium from the intestines to the blood stream
Where is PTH released from?
Chief cells of the parathyroid glands
How does PTH affect calcium levels?
It increases them by…
Increasing bone resorption - binds to osteoblasts and upregulates expression of RANKL which stimulates pre-osteoclasts to differentiate into osteoclasts
Increasing renal reabsorption of calcium - upregulates expression of specific channels in DCT
Increasing synthesis of calcitriol - upregulates expression of 1-alpha-hydroxylase
Where is calcitonin secreted from?
Parafollicular cells in the thyroid gland
How does calcitonin affect calcium levels?
Decreases them by inhibiting osteoclasts = reduces bone resorption
What is osteomalacia?
Softening of the bones secondary to low vitamin D levels = decreased bone mineral content
(Aka rickets in children)
Causes of osteomalacia?
Vitamin D deficiency (malabsorption, lack of sunlight, diet)
CKD
Drug induced e.g. AEDs
Inherited - hypophosphataemic rickets
Severe liver disease
Coeliac disease
Pathophysiology of osteomalacia?
Vitamin D deficiency = lack of calcium and phosphate absorption intestines and reabsorption in kidneys = low calcium and phosphate = defective bone mineralisation = increased PTH secretion by parathyroid glands = increased calcium reabsorption from bones further impairing bone mineralisation
Presentation of osteomalacia?
Bone pain
Bone and muscle tenderness
Fractures - esp femoral neck
Proximal myopathy
Investigations for osteomalacia?
Bloods - vit D and bone profile, LFTs (for ALP) and PTH levels
XR
DEXA scan
(May also try to find cause e.g. U&Es, TFT, coeliac serology)
Some individual factors that affect the amount of vitamin D synthesized in the skin?
Age - lower serum 25-hydroxyvitamin D concentrations in older people
Skin colour - melanin pigment absorbs a proportion of UVB radiation so people with darker skin may need more sunlight exposure to produce the same amount of vitamin D as those with lighter skin
Clothing cover
Sunscreen use
Risk factors for vitamin D defieicny?
Aged over 65
Low or no sun exposure e.g. cover skin, house bound
Darker skin pigmentation
GI or malabsorption disorder
Severe liver disease
CKD
Certain drugs e.g. AED
Pregnant or breastfeeding
Obese
Vitamin D, calcium, phosphate and ALP levels in pts with osteomalacia?
Low vit D
Low calcium
Low phosphate in most
Raised ALP due to increased osteoblasts activity
XR findings in osteomalacia?
Diffuse demineralisation
Insufficiency fractures - looser zones
What are looser zones?
Pseudofractures - a thin translucent band that runs perpendicular to the surface of the bone extending from the cortex inwards
They are incomplete stress fractures which heal with callus lacking in Ca
Most common in pubic rami, neck of humerus/femur, and axillary edge of scapulae
Seen in osteomalacia
Management of osteomalacia?
Vitamin D supplementation - usually a loading regime and then a maintenance dose
Calcium supplementation if dietary calcium is inadequate
What is osteoporosis?
A significant reduction in bone density making them weaker and prone to fractures
When bone mineral density is less than 2.5 standard deviations below the young adult mean density
What is osteopenia?
When bone mineral density is 1-2.5 SD below ythe young adult mean density
I.e. low BMD but not low enough to be classed as osteoporosis
What are fragility fractures?
Pathological fractures that result from low energy trauma
Usually hip, distal radius or spine
Risk factors for osteoporosis?
Older age
Female gender. Particularly post-menopausal women
Reduced mobility and activity
Low BMI (under 19 kg/m2)
Low calcium or vitamin D intake
Alcohol and smoking
Personal or family history of fractures
Chronic diseases (e.g. CKD and RA)
Long-term corticosteroids (e.g., 7.5mg or more of prednisolone daily for longer than 3 months)
Certain medications (e.g., SSRIs, PPIs, anti-epileptics and anti-oestrogens)
Sedentary lifestyle
Premature menopause
Endocrine disorders - hyperthyroidism, hypogonadism, GH deficiency, DM, hyperparathyroidism
Multiple myeloma and lymphoma
GI disorders - IBD and coeliac
Osteogenesis imperfecta
Screening tools used in osteoporosis?
FRAX or QFracture - assess the 10 year risk of a pt developing a fragility fracture
How is bone mineral density assessed?
Using a Dual-energy X-ray Absorptiometry scann that looks at the hip and lumbar spine
How do we interpret DEXA scan results?
They produce either a Z-score or a T-score
A Z-score is the number of SD the pt is from the average for their age, sex and ethnicity
The T-score is the number of SD that the pt is from an average healthy young adult - this is the score used to make the diagnosis
How does a DEXA scan work?
X-rays are used and detectors measure how much radiation passes through the bones and calculate a bone density score
How to interpret T scores from a DEXA scan?
> -1.0 = normal
-1.0 to -2.5 = osteopaenia
< -2.5 = osteoporosis
Epidemiology of osteoporosis?
F:M 6:1
Prevalence in women its at 2% at 50 years, and >25% at 80 years
Medications that can worsen osteoporosis?
Steroids
SSRIs
AEDs
PPIs
Glitazones
Long term heparin therapy
Aromatase inhibitors e.g. anastrazole
Investigtaions for osteoporosis?
FBC, U&Es, CRP, bone profile, albumin, LFTs, TFTs
DXA scan
Others may be indicated e.g. PTH, protein immunoelectrophoresis, serum testosterone, urinary calcium
What amount of steroid is thought to significant raise the risk of osteoporosis?
Taking the equivalent of 7.5mg a day of pred for 3 or more months
Who should be assessed for osteoporosis?
Women >65 and Men >75
Younger pt with risk factors e.g. previous fragility fracture, use of steroids, history of falls, FHx of hip fractures, low BMI, smokers, high alcohol intake
What is the FRAX score?
This estimates the 10 year risk of a fragility fracture occurring
Its valid for pt aged 40-90
It is based on international data so the use is not limited to UK patients
It assesses age, sex, weight, height, fractures, parental fractures, current smoking, steroids, RA, secondary osteoporosis, alcohol intake
You can but BMD into the data which improves the accuracy but this requires a DEXA scan before
Interpreting the FRAX score?
If done without BMD it will be categorised as…
Low risk - reassure and give lifestyle advice
Intermediate risk - offer BMD test
High risk - offer bone protection Tx
If done with a BMD it will be categorised as…
Reassure
Consider Tx
Strongly recommend Tx
Managing a pt following a fragility fracture?
For pt who had a fragility fracture…
>=75 - presumed to have underlying osteoporosis so Tx
If <75 then arrange a DEXA scan, enter into FRAX score and this will determine Tx
Presentation of osteoporotic vertebral fractures?
Often asymptomatic and found incidentally
Acute back pain
Breathing difficulties
GI problems due to compression of abdominal organs
Falls/trauma
Loss of height
Kyphosis
Localised tenderness on palpation of spinous processes at the fracture site
XR of spine findings in osteoporotic vertebral fractures?
Wedging of vertebrae
May also show old fractures which appear sclerotic
What is secondary osteoporosis?
Decreased BMD or fragility fractures affecting people who have a secondary cause for bone loss e.g. CKD, coeliac, hyperthyroidism, drugs
Describe bone mineral density over the ages in men and women?
In childhood and adolescence BMD rapidly increases and reaches the peak by 20-30. Men reach a higher peak than women
After this BMD remains relatively stable provided bone formation and resorption is maintained e.g. weight bearing exercises and sufficiency vitamin D & Ca intake
After the age of 30 BMD declines gradually.
After menopause women experience a significant drop in BMD
In later adulthood men and women continue to experience a gradual decline in BMD. The decline is generally more gradual and starts later than in women
Why does menopause significantly impact BMD?
Oestrogen inhibits osteoclasts and stimulates osteoblasts
When oestrogen levels decline at menopause the balance between bone formation and resorption is disrupted and there is an increase in osteoclast activity = greater risk of osteoporosis
In which pt is treatment for osteoporosis indicated?
Following osteoporotic fragility fractures in post-menopausal women confirmed with osteoporosis OR pts over 75
Why can 25% of patients not tolerate alendronate?
Due to upper GI problems - indigestion or oesophagitis
management of osteoporosis?
Lifestyle changes - increase physical activity, stop smoking, maintain normal BMI, reduce alcohol
Adequate intake of Ca and vit D - supplements may be necessary
Bisphosphonates - oral alendronate or risedronate sodium are first line
HRT may be considered in post menopausal women
Others: raloxifene, strontium ranelate, denosumab, teriparatide
How do bisphosphonates work?
They are analogues of pyrophosphate which is a molecule that decreases demineralisation in bone by inhibiting osteoclasts
Which bisphosphonates can be given IV?
Zoledronic acid - once yearly
How should oral bisphosphonates be taken?
On an empty stomach with a full glass of water
After the pt should sit upright for 30 mins to reduce risk of reflux and oesophageal erosions
Side effects of bisphosphonates?
Oesopheagitis and oesophageal ulcers
Osteonecrosis of the jaw - esp with IV bisphosphonates
Increased risk of atypical stress fractures
Acute phase response following administartion e.g. fever, myalgia, arthralgia
Osteonecrosis of the external auditory canal - ear infection Sx
Duration of bisphosphonate treatment?
Varies according to the level of risk
Some recommend stopping them at 5 years if pt is <75, femoral neck T-score is >-2.5 and low risk according to FRAX
Why can bisphosphonate treatment cause atypical fractures?
As bisphosphonates cause bone to harden but alter the cortical composition which makes them more brittle
which bisphosphonates are most likely to cause oesophagitis?
Oral alendronic acid
What is Osteonecrosis of the jaw?
A severe bone disease that causes death of the jaw - causes exposure of mandibular or maxillary bone through lesions in the gingiva
Its most frequent after invasive dental procedures (so before pts go on bisphosphonates they will have to have any pending dental procedures asap)
It is associated with bisphosphonate therapy
What is Paget’s disease of the bone?
A disease of increased, uncontrolled bone turnover
Its a disorder of osteoclasts - excessive osteoclastic resorption
Its common in the UK but only symptomatic in 1 in 20 pt
Where in the body is Paget’s disease most likely?
Skull
Spine
Pelvis
Long bones of lower extremities
Risk factors for Paget’s disease?
Older age
Male
Northern latitude
FHx
Clinical features of Paget’s disease?
Older male with bone pain and isolated raised ALP
Bone pain is commonly pelvic, lumbar spine and femur
If untreated it can cause bowing of the tibia and bossing of the skull
Investigtaions for Paget’s disease?
Bloods - LFTs (raised ALP), bone profile (Ca and phos normal)
Other markers of bone turnover e.g. PINP, CTx, NTx, urinary hydroxyproline
XR - osteolysis and changes in skull XR e.g. thickened vault
Bone scintigraphy - increased uptake will be seen focally at sites of active bone lesions
Indications for treating Paget’s disease?
Bone pain
Skull or bone deformity
Fractures
Periarticular pagets
Management of Paget’s disease?
Bisphosphonates
Complications of Paget’s disease?
Deafness - CN entrapment
Bone sarcoma
Fractures
Skull thickening
High-output HF
Pagets vs osteoporosis?
Osteoporosis causes thin, fragile bones
Paget’s disease causes enlarged, deformed bones
