Osteoporosis Flashcards
Bone remodelling
Bone is constantly remodelled.
Balance of reabsorption and formation.
Osteoclasts are cells that reabsorb bone by “digging” pits, while osteoblasts secrete bone matrix into these pits, called osteoid. Osteoid is then mineralised, resulting in calcium phosphate crystals being deposited.
Calcium in the bones
Bone is made from Ca, Phosphate, protein meshwork.
Serum Ca2+ ion concentration is controlled by parathyroid hormone (PTH) secreted from the parathyroid glands found behind the thyroid gland in the neck.
PTH is secreted in response to low serum Ca2+ ion levels. It acts on the kidneys to reabsorb Ca2+ ions and to stimulate the activation of vitamin D. This fat-soluble vit D is obtained from sun exposure certain foods, and supplements but is biologically inert must be activated. Activated vit D promotes absorption of dietary Ca2+.
PTH also acts directly on bone to mobilize Ca2+ (transfer Ca2+ from bone to the blood).
Calcitonin, secreted from parafollicular cells (also known as C cells) in the thyroid gland, inhibits calcium mobilisation from bone and also decreases reabsorption from the renal tubule.
Definition & Causes
Osteoporosis is a reduction in actual bone mass. = more fractures and broken bones
Osteopenia is a reduction in the mineral content of bone
CAUSES =
*Postmenopausal oestrogen deficiency
*Age-related deterioration in bone homeostasis
*Long term levothyroxine use. Subclinical hyperthyroidism may be associated with bone loss. To minimise the risk of osteoporosis, dosage of levothyroxine sodium should be titrated to the lowest possible effective level.
*Prolonged glucocorticoid use
*Myeloma (a type of cancer that develops from cells in the bone marrow)
Assessment (WHO) (fragility fracture risk) (don’t need know)
18+ only
Find high risk groups:
Women >65, men >75
Women 50 - 64 and men 50 to 74 with these risk factors:
previous osteoporotic fragility fracture, using or frequently used oral corticosteroid, history of falls, low BMI, smoker, >14 units a week of alcohol, or any1 with Secondary causes of Osteoporosis =
Hypogonadism, including untreated premature menopause, treatment with aromatase inhibitors (such as exemastane) or GnRh (eg goserelin).
Endocrine conditions, including diabetes, Cushing’s disease, hyperthyroidism, hyperparathyroidism, and hyperprolactinaemia.
Conditions associated with malabsorption, including IBD, coeliac disease, and chronic pancreatitis.
RA and other inflammatory arthropathies.
Haematological conditions such as multiple myeloma and haemoglobinopathies.
COPD.
Chronic liver failure.
Chronic kidney disease.
Immobility.
<50 years old:
using or frequently used oral corticosteroid, untreated premature menopause, previous fragility fracture,
<40 years old:
using or recurrent use of high-dose oral corticosteroids = to >7.5 mg prednisolone daily for 3 months or +, Previous fragility fracture of the spine, hip, forearm, or proximal humerus, History of multiple fragility fractures
Consider assessing if using:
SSRI, Antiepileptic (mainly enzyme 1s like carbamazepine), aromatase inhibitors (exemastane), GnRh agonists (eg goserelin), PPI, Thiazolidinedione’s (eg pioglitazone)
Assessment (HOW) (fragility fracture risk) (don’t need to know)
Exclude non-osteoporotic causes for fragility fractures:
metastatic bone disease
multiple myeloma
osteomalacia
Paget’s disease
Exclude secondary causes of osteoporosis:
Endocrine conditions such as untreated premature menopause in women, hypogonadism in men, diabetes mellitus, hyperthyroidism
Rheumatological conditions such as rheumatoid arthritis, and other inflammatory arthropathies
GI conditions that cause malabsorption such as CD, UCs, coeliac disease, chronic pancreatitis
Chronic liver disease
COPD
Offer DXA scan to measure bone mineral density (BMD) without calculating the fragility fracture risk for:
>50 with history of fragility fracture
<40 with major risk factor for fragility fracture
{DRUGS CAN BE STARTED WITHOUT SCAN FOR VETEBREAL FRACTURE}
For all other people with risk factors for osteoporosis, calculate the 10-year fragility fracture risk BEFORE a DXA scan to measure BMD:
Measure BMD + DXA in ppl with high risk of fragility fracture or fracture risk is near threshold.
Asses VIT d deficiency and poor calcium intake. (1g/day reccomended for increased risk of fracture ppl)
Identity risk factors for falls
Qfracture and FRAX the tools used.
10 year fracture risk of 10% is the threshold for doing a DXA.
RISK Qfracture FRAX
HIGH >10% RED
MEDIUM close but <10% Orange
LOW <10% Green
Treatments
Combination of lifestyle changes + drug treatment = aims to prevent fragility fractures in patients.
NON Pharmacological
Increase physical activity
Stop smoking
Maintain normal BMI (20–25 kg/m²)
Reduce alcohol intake (improves bine health and reduces risk of fracture)
Good intake of calcium and VIT D
Calcium through diet or supplements if needed. (Seeds, cheese, yoghurt, salmon, beans/lentils, almonds, etc)
Vit D can be through diet too if needed (Oily fish, sardines, salmon, egg yolk, red meat, liver)
Pharmacological
Low risk = no drugs
Medium/High = if T score is <-2.5 (osteoporosis range) offer bone sparing drugs treatment. T score >-2.5 - modify risk factors and treat conditions then repeat DXA when appropriate.
1ST LINE =
Bisphosphonate = alendronate 10 mg OD or 70 mg OW, or risedronate 5 mg OD or 35 mg OW.
contraindicated = ALT - referral
If Adequate calcium intake (700mg/day) = 10mcg of VIT D daily for ppl with less sunlight exposure
If Poor calcium intake = 10mcg VIT D + 1g Calcium daily
OR 20mcg VIT D + 1g calcium daily for elderly/ living in nursing home.
Consider HRT to younger post menopausal women
post menopausal women
1st line is same.
ALT oral ibradronic acid or parenteral denosumab
Bisphosphonate ALT = raloxifene or strontium.
HRT (Tibolone) additional ALT.
SEVERE or high risk of fracture = teriparatide or romosozumab
Follow up on Treatment
At med review ask about AE: upper GI, Atypical fracture symptoms (hip, groin, thigh pain)
Ask on adherence.
Ppl on Oral corticosteroid continue treatment with bisphosphonates and/or VIT D and calcium until corticosteroid has stopped.
Other ppl review need for continuing with bisphosphonates after 3- 5 years:
Remain HIGH risk continue treatment with alendronic acid for up to 10 years, and risedronate for up to 7 years. Includes ppl with any of the following risk factors:
Age >75 years.
A previous hip or vertebral fracture.
Other ppl arrange DXA and continue if T score <-2.5. reassess BMD every 3-5 years. stop if BMD T score is >-2.5 and reassess BMD after 2 years.
Ppl whose fracture risk was intermediate last time they were assessed, reassess after a minimum of 2 years.
Drugs and MOAs (background info)
HRT - oestrogen replacement - effective but this is not selective, which means it can have effects on many body systems.
SERMs - (Raloxifene) - agonist actions on some tissues and antagonist actions on others
Mechanisms include:
* Increased osteoblast activity in a dose-dependent manner,
* Reduced activity of osteoclasts.
* extensive first-pass metabolism, well distributed around the body.
PTH and PTH fragments - teriparatide): Increase bone mass by paradoxically stimulating osteoblast numbers and decreasing osteoblast apoptosis. They act on PTH-1 receptors (GPCR), activating adenylate cyclase, PLA2, PLC and raise intracellular Ca2+ levels. These are given subcutaneously
Bisphosphonates (alendronate and risedronate): These act on osteoclasts to promote their apoptosis, inhibiting bone reabsorption. Usually given orally and accumulate at site of bone mineralisation.
Absorption can be impaired by certain foodstuffs, especially milk, and these drugs can cause severe GI disturbances. So, patients are usually instructed to remain upright after taking for 30 mins, to ensure that the drug has passed into the stomach so as to minimise ulceration of the trachea
Drugs counselling/ info
Bisphosphonates:
Contraindications - hypocalcaemia or other disturbances of bone and mineral metabolism - Treat b4 starting drugs
- severe CKD
- Unable to sit or stand upright for 30 mins or oesophagus issues.
- P or BF
AE: GI, oesophagus issues, osteonecrosis of jaw or ear canal.
KEY interactions:
- calcium supplements, antacids, and food and drink (decrease bioavailability) [leave 30 mins between taking drug and any of these].
- NSAID - caution Higher risk of GI issues
COUNSELLING:
- Take on empty stomach, Risderonate best to take 30 min b4 breakfast otherwise should be taken 2 hrs b4 other meals. Alendronate 30 mins b4 FIRST food.
- swallow whole with water stay upright for 30 min. Once weekly take same day every week.
- if A missed then skip dose for the day on OD. IF R misssed take when next possible (as above)OD
- OW - Take asap never take 2 tabs a day.
- get dental check uo b4 stating drug.
Calcium & VIT D Preps
contraindications:
- Any disease or condition that results in hypercalcaemia and/or hypercalciuria (Hyperparathyroidism.
Renal stone disease, Ckd 4/5 Hypervitaminosis D, Allergy to peanuts/soya
AE: GI, Hypercalciuria
KEY interactions:
- Oral bisphosphonates
- Quinolones, Tetracyclines AND Levothyroxine, iron, zinc = reduce absorption. Q & others 2 hrs B4 calcium. T 2/3hrs b4 calcium.
- Digoxin = increase D effects
- Thiazide diuretics = reduced urinary calcium excretion
- Oral corticosteroids = reduced calcium absorption
- Phenytoin or barbiturates (long-term use) = decrease VIT d effects.
