Osteoporosis, calcium, vit D, phos Flashcards
Risk factors for OP
FHx Female Previous minimal trauma # Post menopausal Late menarche, early menopause Age Glucocorticoids Androgen deprivation therapy (prostate ca) Aromatase inhibitors (breast ca) Smoking ETOH+++ Physical inactivity Low calcium intake Vitamin D deficiency Low protein intake Low body weight CT disease Haematological disorders Chronic disorders e.g. CKD
Endocrine disorders e.g. sex hormone deficiency, cushing’s, hyperthyroidism, hyperparathyroidism, DM
Malabsorption disorders e.g. coeliac, bariatric surgery
How is OP diagnosed?
1) Fragility fracture after age 50 - any fracture other than fingers, toes, skull, face. Particularly in the spine, hip, wrist.
OR
2) BMD measurement
- T-score ≤-2.5 is consistent with osteoporosis, whereas a T-score between -1 and -2.5 is low bone mass (osteopenia)
What’s the fracture risk assessment tool?
In the US, diagnosis of OP can be made calculating the absolute fracture risk.
In Australia, using this score to guide treatment is grade D evidence, and not covered by PBS.
What’s the Z score?
Z score compares your bone density to the average person your age and gender
Initial Investigations for OP
25OHD, CMP, renal function, liver function, TSH
BMD (DXA)
Thoracic and lumbar spine xray (in selected cases)
Further investigations SPEP FLC/urine bence jones protein PTH TSH ESR CRP Testosterone (males only) Coeliac screen Estrogen FSH/LH Hypercorticolism screen 24h urine calcium and creatinine excretion
What’s a fracture risk calculator?
FRAX and GARVAN most commonly used
- Primarily driven by BMD, age, previous #
Calculates 10 year probability of fracture at hip or any site
What’s a trabecular bone score?
Has a role in fracture risk assessment
Low TBS is associated with increased fractures
Its a texture analysis, related to bone microarchitecture
Compares adjacent areas of bone to each other. When there is a bigger difference between adjacent bone the trabecular bone score will be worse
When is antiresorptive medication subsidised by PBS for OP?
1) Minimal trauma fracture regardless of BMD
2) 70 years + OP at spine or hip
3) T score ≤-2.5
Rx OP
Antiresorptive therapy Vitamin D Calcium Exercise - weightbearing exercise Smoking cessation
Which antiresorptive medication do we use for post-menopausal women?
Start with PO bisphosphonates - alendronate or risedronate
Which antiresorptive medication should we use in patients with oesophageal disorders, GI intolerance to PO bisphosphonates, inability to remain upright after dose?
IV bisphosphonate - zoledronic acid is preferred
When to follow up after commencing anti-resorptive therapy?
DEXA hip and spine after 2 years
If BMI is stable or improved, less frequent monitoring thereafter
Risks with bisphosphonates
Atypical femoral fractures*
- Prodrome with thigh pain; 1/3 bilateral
- Need xray or bone scan
- SE Asian women are most at risk
- Rx: stop antiresorptive therapy (risk of contralateral femur), surgery
Osteonecrosis of the jaw*
- Exposed alveolar bone
- Confirmed: >8 weeks after extraction
- Rx: stop antiresorptive therapy, daily antimicrobial rinses, abx, occasionally surgical debridement
*Both risks increase with duration
Oesophagitis
Risk with denosumab
Rapid loss of bone and increased risk of spontaneous vertebral # if dose delayed by 4 weeks so need continuous lifelong therapy
Hypocalcaemia particularly in impaired kidney function, vitamin D deficiency or a malabsorptive disorder
Osteonecrosis of the jaw
When to do BMD testing?
> 70 years
After minimal trauma fracture
Comorbidities
Management post minimal trauma fracture
Minimal trauma hip fracture in post menopausal woman (or man >50 years) = treat
“Asymptomatic” vertebral fracture = treat
How to take oral bisphosphonates?
Empty stomach
At least 2 hours apart from calcium, iron, magnesium, antacids (can limit absorption of bisphosphonate)
What’s raloxifene and when is it used?
Selective estrogen receptor modulator
Reduces post menopausal bone loss, risk of breath cancer
Most appropriate for younger postmenopausal women (<60 years) with spinal OP
What’s tibolone and when is it used?
Oestrogenic effects on bone
Reduces risk of # in postmenopausal women (similar extent to estrogen therapy)
Used for women <60years with menopausal symptoms but not explicitly for OP
What’s teriparatide and when is it used?
Synthetic form of PTH. Increases bone formation.
Reduces incidence of vertebral and nonvertebral fractures in postmenopausal women.
Increases BMD
Very strict PBS criteria (must be started by a specialist)
- T score of -3 or less
- At least 2 minimal trauma fractures, including a fracture after at least one year of antiresorptive therapy
When can you not use teriparatide?
<25 years old
Known or suspected Paget disease of bone
Previous radiotherapy involving bone
Pre-existing hypercalcaemia, malignancy, severe kidney disease or primary hyperparathyroidism
How long can you use teriparatide for?
Max 24 months in one lifetime
When can you not use bisphosphonates?
Severe kidney disease
What’s osteonecrosis?
Avascular necrosis of bone
Causes of osteonecrosis
Steroid use
Alcoholism
Bisphosphonates
SLE
What increases your risk of osteonecrosis of the jaw with bisphosphonates?
If bisphosphonates are used to treat metastatic cancer or plasma cell myeloma (rather than OP)
IV administration
Dose and duration of exposure
Dental extractions, implants, poorly fitted dentures, preexisting dental disease
Glucocorticoids
Smoking
Diabetes
How does osteonecrosis present?
Pain, swelling, exposed bone, local infection, pathological fracture of the jaw
When should we withhold bisphosphonates?
Prior to many dental procedure and don’t restart until after healing
Do you need a dental visit before starting bisphosphonates?
No
Explain calcium homeostasis. How does calcium, vitamin D and PTH work?
Low serum Ca2+ –> increased PTH (from parathyroid gland)
PTH
- Increases bone osteoclast activity –> releasing Ca2+ and phos
- Increases renal conversion of 25-hydroxycholecaiferol to 1,25-dihydroxycholecalciferol –> increases small bowel absorption of Ca2+ and phos
- Increases renal calcium reabsorption (distal tubule) and decreases phosphate reabsorption (proximal tubule)
= Ultimately increases Ca2+ back to normal
How is calcium transported in the blood?
45% bound to protein (mostly albumin)
15% bound to phosphate and citrate
40% ionised state
Which part of calcium is metabolically active?
Only ionised calcium
What’s pseudohypocalcaemia?
When the total calcium is low but the ionised calcium is normal
Can happen in low protein (nephrotic syndrome, malnutrition, chronic illness), fluid overload
How does pH affect calcium levels?
Acidosis reduces binding of calcium to albumin
Alkalosis enhances
Causes of hypercalcaemia
90% caused by hyperparathyroidism or malignancy
PTH dependent
1) Excess PTH
- Primary parathyroid tumours (adenomas, hyperplasia, carcinoma) or tertiary
- Familial hypercalciuric hypercalcaemia - impaired Ca2+ sensing in parathyroid glands/kidneys
- Ectopic PTH (rare)
PTH independent
2) Malignancy
- PTHrP (PTH mimic)
3) Excess 1,25 vitamin D
- Granulomatous disorders (sarcoid, TB, silicosis)
- Lymphoma
- Vitamin D intoxication
4) Increased bone resorption
- Multiple myeloma, thyroxicosis, immobilisation, vitamin A toxicity, osteolytic metastasis
5) Endocrine - adrenal insufficiency, pheochromocytoma
6) Medications
- Lithium - alters calcium sensing receptors at the parathyroid and kidneys –> increases PTH release and Ca2+ reabsorption from kidneys
What is familial hypocalciuric hypercalcaemia?
Inherited condition
Mutation in the calcium sensing receptor gene expressed in parathyroid and kidney tissue –> impaired Ca2+ sensing –> ongoing PTH release and Ca2+ reabsorption from the kidneys despite hypercalcaemia –> hypercalcaemia
Investigations in hypercalcaemia
Always measure PTH first +/- urinary calcium excretion +/- vitamin D metabolites
> If elevated or high normal –> likely primary hyperparathyroidism; consider familial hypercalciuric hypercalcaemia –> Measure urinary calcium excretion –> if high, its primary hyperparathyroidism; if low, its FHH
> If low –> measure PTHrP and vitamin D metabolites
- Elevated PTHrP –> scan for malignancy
- Elevated 1,25D –> CXR (lymphoma, sarcoid)
- Normal PTHrP, vit D –> consider other causes (measure SPEP, UPEP, TSH, vitamin A)
- Elevated 25D –> check medications
How does cinacalcet work?
Binds to the calcium sensing receptor (parathyroid) and tricks it into thinking there is more calcium than there is –> reduce PTH release –> reduce calcium
