Metabolic bone disease Flashcards
Which cells create new bone during bone remodelling cycles?
Osteoblast
Which cells break down bone during bone remodelling cycles?
Osteoclasts
Bone remodelling occurs all the time in the human skeleton but at different rates depending on what?
The age of the individual and their clinical circumstances (i.e co-morbidities)
Factors that influence bone turnover
PTH - parathyroid hormone
Vitamin D
Interleukins - cytokines (secreted proteins and signal molecules) such as in rheumatoid arthritis
Effective steroids
Where is vitamin D stored in the body?
Liver
Fat
Muscle
What is the active form of vitamin D called and where is it metabolised?
Calcitriol - 1,25(OH)2 Vit D
The kidney
What is the main function of vitamin D in the body?
Absorption of calcium and phosphate from the gut.
It then works with PTH to move Ca2+ in and out of tissues and to store it.
What is the test used to measure vitamin D levels in the body?
25-hydroxyvitamin D
Why might someone have low calcium levels in the body?
Liver or kidney disease
Darker skin (melanocytes compete for uv radiation and prevent initial chemical reaction)
Older people (less 7 DHC (dehydrocholesterol) in skin so harder for them to make vitamin D)
Geographical distribution (living away from the equator have seasoned vitamin D production – we store vitamin D throughout this time so that we can use it all year round)
What is Paget’s disease?
A disease where there is interference with the body’s normal bone turnover processes.
Increased bone resorption followed by increased bone formation
Leads to disorganised bone - bigger, less compact, more vascular and more susceptible to deformity and fracture
Who gets Paget’s disease?
Patients are always over 40 years old but commonly over 60.
Strong genetic component - 15-30% familial
Restricted geographic distribution: commonly found in the UK, Australia, East coast of America etc
Environmental trigger - possibility of chronic viral infection within osteoclast celsl
Symptoms of Paget’s disease?
Deep seated bone pain
Occasionally presents with bone deformity
Excessive heat over the Pagetic bone (tends to be long bones but also pelvis and skull)
Neurological complications i.e nerve deafness - only occurs if there is paget’s in the skull bone
Which investigation is good for Paget’s disease?
An isotope bone scan - shows the spread of Paget’s throughout the skeleton
X-ray good too
What is the most common presentation of Paget’s?
An isolated elevation of alkaline phosphatase on blood test. Should not treat on this alone though.
Any condition of bone growth or an increased activity of bone cells, including Paget disease, will cause alkaline phosphatase levels to rise.
What is a rare presentation of Paget’s?
Osteosarcoma in affected bone
Treatment for Paget’s disease?
1st line = IV Bisphosphonate therapy - a one off infusion of zoledronic acid
Oral bisphosphonate is also suitable but not tolerated as well
NSAIDs for bone pain
Calcium and vitamin D supplementation, particularly whilst on bisphosphonates
If a Paget’s patient is asymptomatic what would be the only reasons to treat them?
If their skull is affected
Or if they require surgical intervention for something i.e a hip replacement - this proves difficult in a pagetic bone as it’s very vascular and the surgery would be easier when the paget’s disease was quiet
Otherwise, these patients can be safely ignored in most cases
What causes Rickets (in children) and Osteomalacia (in adults)?
Severe nutritional vitamin D or Calcium deficiency which causes insufficient mineralisation
Osteomalacia occurs when the epiphyseal lines are closed
Symptoms associated with Rickets in children?
Large skull (large forehead) Stunted growth Bowing of the legs (odd-shaped) Large abdomen Odd-shaped ribs and breast bones Wide bones Odd curve to spine or back
Osteomalacia
Most common in elderly especially those institutionalised or house bound
symptoms - bone pain, muscle weakness, increased fall risk
Sometimes see microfractures on x-ray particularly on pelvis, ribs or long bones
What is Osteogenesis Imperfecta?
A genetic disorder of connective tissue (collagen type 1)
Causes fragile bones from mild trauma and even acts of daily life
There are other non-bone clinical features as type 1 collagen is found in other tissues
Broad clinical range - from those which are prenatally fatal to those only presenting in 40s
There are 8 types - first 4 are more common though
Other than fragile bones what are the other features of Osteogenesis Imperfecta?
Growth deficiency
Defective tooth formation (dentigenesis imperfecta)
Hearing loss
Blue sclera – white of the eye appears blue
Scoliosis / Barrel Chest
Ligamentous laxity - hypermobility
Easy bruising
How is osteogenesis imperfecta managed?
Surgical - treat fractures
Medical - prevent fractures using IV Bisphosphonates
Social - educational and social adaptations
Genetic - counselling for parents and next generation
How is Osteoporosis defined?
A metabolic bone disease characterised by low bone mass and micro architectural deterioration of bone tissue
This leads to enhanced bone fragility and a consequent increase in fracture risk => this is key
What are 2 common calculator tools used to assess fracture risk?
FRAX - used worldwide
Q fracture - used in the UK
Which scanning technique is used to assess patients with a FRAX or Q fracture score greater than 10% / those on oral steroid medication / those with a low trauma fracture?
DEXA scan (Dual energy X-ray Absorptiometry) - a low radiation technique
When doing a DXA scan what does it mean by the patient’s T and Z score?
T score = Compares the patient to a young adult. It shows the number or standard deviations the patient is below that of the young adult range (the group of patients should be of the same sex, ethnicity and BMI – the only difference must be age). For ever SD you fall below the young adult range there is a doubling of the risk of a low trauma fraction
Z score = compares the patient with an age-matched individual and determines whether their result is expected for their age. You would hope your Z score would be 0 throughout your life.
Who is at risk of Osteoporosis?
MANY PEOPLE
I in 2 women over 50 will have an osteoporotic fracture before they die
I in 5 men over 50 will suffer an osteoporotic fracture
Endocrine causes of Osteoporosis
Thyrotoxicosis - clinical syndrome of excess circulating thyroid hormones, irrespective of the source
Hyper and Hypoparathyroidism
Cushings disease
Hyperprolactinaemia
Hypopituitarism
Low sex hormone levels – early menopause, use of GnRH inhibitors
Rheumatic causes of Osteoporosis
Rheumatoid arthritis
Ankylosing Spondylitis - sero-negative RA
Polymyalgia Rheumatica
GI causes of Osteoporosis
Inflammatory diseases: UC and crohns
Liver diseases: primary biliary cirrhosis, Alcoholic cirrhosis, Viral cirrhosis (Hep C)
Malabsorption: Cystic Fibrosis, chronic pancreatitis, coeliac disease, whipples disease, short gut syndromes and ischaemic bowel
Medications which cause osteoporosis
Steroids
PPI - proton pump inhibitors - decrease intestinal absorption of calcium
Enzyme inducting anti-epileptic medications e.g carbamazepine, phenytoin - reduces amount of vitamin D in the body
Aromatase inhibitors - hormone therapy
GnRH inhibitors - Gonadal steroids drive the significant bone mineral increase that occurs at puberty. Oestrogen deprivation in women results in bone loss.
Warfarin
How does our bone mass change during our lifetime?
Peak height at end of puberty
Still accrue bone mass after this but at a slower pace
Late 20s – peak bone mass
This is maintained until 40s roughly
Accelerated loss begins at menopause
How can osteoporotic fractures be prevented?
Minimise risk factors - smoking, alcohol, steroid use
Ensure good calcium and vitamin D status
Falls prevention
Medications - bisphosphonates
Which medications are used to manage osteoporosis?
Bisphosphonates - 1st line generally
Hormone replacement therapy (HRT) - excellent at reducing spine, hip and peripheral fractures.
Selective oEstrogen Receptor Modulator (SERM)
Denosumab
Teriparatide
Side effects of HRT
Increased risks of blood clots
Increased risk of breast cancer with extended use into late 50s/early 60s
Increased risk of Heart disease and stroke if used after large gap from menopause
Which type of Selective estrogen receptor modulators (SERM) drug is used for osteoporosis?
Raloxifene - reduces risk of vertebral fractures only
Negative effects of SERMS
Hot flushes if taken close to menopause
Increased clotting risks
Lack of protection at hip site - doesn’t prevent hip fractures
What is needed first before starting a patient on Bisphosphonates for osteoporosis?
Adequate Renal function required
Adequate Calcium and Vitamin D status
Good Dental Health and Hygiene advised
Side effects of Bisphosphonates
Heart burn
Osteonecrosis of the jaw - if jaw bone becomes exposed and infected
Oesophagitis
Iritis/uveitis
Not safe when eGFR <30mls/min
Atypical femoral shaft fractures
What is Denosumab?
A RANK Ligand inhibitor that alters osteoclast differentiation and activation. In this case, it reduces osteoclastic bone resorption
Patient’s get a subcutaneous injection every 6 months - this reduces bone breakdown and helps to strengthen bones
Safer in patients with significant renal impairment than bisphosphonates
Reduces fracture risk
What is Teriparatide?
A form of parathyroid hormone used to treat osteoporosis - works by increasing osteoblast activity
side effects = injection site irritation and allergy
