Seminar C Osteoporosis Flashcards
Trabecular bone action →
- Calcium reservoir
2. Site of haematopoiesis
Bone consists of
osteoid, a collagenous organic matrix, (organic phase) on which is deposited complex inorganic hydrated calcium salts known as hydroxyapatites (mineral phase)
Organic Phase
type 1 collagen and other non-collagenous proteins e.g.osteocalcin
Bone turnover mediated by
Cytokines (not completely sure)
Bone formation requires
osteoid synthesis and adequate calcium and phosphate for the laying down of hydroxyapatite
Osteoblasts secrete
Alkaline phosphatase - is essential to the process, probably acting by releasing phosphate from pyrophosphate.
Bone acts as important reservoir of
calcium, phosphate and, to a lesser extent, magnesium and sodium
Osteoblasts produce
Osteoid
Systemic Hormones bone control
PTH
Vitamin D
Oestrogen
Growth hormone
Local hormones bone control
Osteoclast regulatory e.g. OSF
Osteoblast regulatory e.g. Wnt signaling
Parathyroid Hormone → Secreted in response to
Plasma ionised Calcium
Parathyroid Hormone →PTH Function
Increase plasma calcium concentration and reduce plasma phosphate.
Parathyroid Hormone →PTH action on Kidneys
Increases the tubular reabsorption of calcium in the kidneys.
Parathyroid Hormone →PTH action on bone
Releases calcium into the ECF, and so increases the amount of calcium filtered by the glomeruli.
Calcitonin →
is a polypeptide hormone produced by C cells of the thyroid. Experimentally it can be shown to inhibit osteoclast activity, and therefore bone resorption, but it is not known if this has any physiological significance.
Calcium Sensing Receptors → Receptor Type
G protein coupled receptor
Calcium Sensing Receptors → Function
Regulates the secretion of parathyroid hormone and the reabsorption of urinary calcium and therefore plays an important role in extracellular calcium homeostasis.
Calcium Sensing Receptors → Clinical disorders associated with abnormalities of receptor
- Familial benign hypocalciuric hypercalcaemia
- Neonatal severe hyperparathyroidism
- Autosomal dominant hypocalcaemia
Metabolic Bone Diseases
- Rickets and Osteomalacia
- Hypocalcaemia and Hypercalcaemia
- Paget’s disease
Rickets:
is defective mineralization of bones before epiphyseal closure in immature mammals due to deficiency or impaired metabolism of vitamin D, phosphorus or calcium, potentially leading to fractures and deformity.
Osteomalacia:
is the softening of the bones caused by defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium, or because of overactive resorption of calcium from the bone as a result of hyperparathyroidism (which causes hypercalcemia).
Common Cause →metabolic bone disease
Vitamin D deficiency
Impaired hydroxylation of Vitamin D
Vitamin D resistance
Vitamin D deficiency
Reduced sunlight exposure
Malabsorption
Dietary deficiency
Impaired hydroxylation of Vitamin D
Chronic renal failure (Most common)
Chronic liver failure
Vitamin D resistance
Hypophosphataemic e.g. oncogenic osteomalacia Sex linked hypophosphataemic rickets Renal tubular disorders Hypophosphatasia Drugs (e.g. epileptics), toxins
Clinical presentation: of metabolic bone disease
- Bone pain
- Skeletal deformity
- Muscle weakness
Childhood onset (Rickets)
clinical picture
- Widened and irregular epiphyses
- Bowing of long bones (bow legs)
- Rib deformities - the inward pull of the diaphragm produces a groove in the rib cage.
Adult onset - symptoms tend to be more vague metabolic bone disease
- Bone pains
- Proximal muscle weakness
- Waddling gait
Symptomatic hypocalcaemia in severe cases causes
- Convulsions
- Tetany
- Cardiac arrhythmias
Investigations:
Xrays
Bloods
Xrays show in osteomalacia
a. Looser’s zones in osteomalacia
b. Bowed legs and widened epiphyses in rickets)
Bloods → in metabolic bone disease show
- Corrected calcium lower end of normal or frank hypocalcaemia in severe cases
- Secondary hyperparathyroidism frequently develops to compensate for the low calcium
- low serum phosphate, elevated PTH, elevated alkaline phosphatase
Treatment: of rickets
Dietary defiency Oral vitamin D (Cholecalciferol)
Malabsorption Paraentral vitamin D
Renal failure Alfacalcidol (1 alpha hydroxyl vitamin D)
What causes rickets and Osteomalacia?
Inadequate activity of vitamin D.
This can be due to vitamin D deficiency, impaired hydroxylation of vitamin D, or resistance to vitamin D.
What are the main clinical features?
The main symptoms are bone pain, skeletal deformity and muscle weakness.
Children with rickets may have bowed legs and rib deformities.
What might you find on x-rays?
Loosers zones, widened and irregular epiphyses, bowed long bones.
How do blood tests differ between osteomalacia and osteoporosis?
Blood tests are normal in osteoporosis.
In Osteomalacia corrected calcium is normal or low, and secondary hyperparathyroidism often develops.
What is the general aim of treatment?
Replace the vitamin D.
Definition osteoporosis
Osteoporosis is a bone disorder featuring progressive loss of bone tissue and bone mass leading to weakening of bone. In osteoporosis, the total mass of bone is reduced, but there are a few other abnormalities. It results from the progressive imbalance between bone resorption and bone formation that is a feature of normal ageing. Some degree of osteoporosis is inevitable in all elderly patients.
→ normally in trabecular bone
Osteoporosis Characterised by
by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and an increase in fracture risk. Bone is normally mineralised but is deficient in quantity, quality and structural integrity.
Bone remodelling →
process (6)
- Begins with recruitment of osteoclast precursors to the remodelling unit, where they differentiate into mature osteoclasts.
- Triggered by mechanical stimuli or release of chemotactic factors from micro fractures in damaged bone.
- During the phase of bone resorption, osteoclasts remove a specific amount of bone, and they then undergo programmed cell death (apoptosis) in the reversal phase.
- Bone formation follows on from the reversal phase, beginning with recruitment of osteoblast precursors to the remodeling site.
- These cells then differentiate into mature osteoblasts and start to form new bone matrix (osteoid), which subsequently becomes calcified to form mature bone.
- Some osteoblasts become buried in the newly formed bone matrix to form osteocytes, which interconnect with each other and with lining cells on the bone surface.
Factors affecting peak bone mass →
- Genetic factors strongly influence bone mass, accounting for 70-80% of its variance.
- Sex hormone status
- Nutrition
- Physical activity
Factors affecting Bone loss →
• In women, oestrogen deficiency is a major pathogenic factor in menopausal bone loss.
• In men, the relationship between age-related bone loss and declining testosterone levels is less well documented.
• In the elderly, vitamin D insufficiency and secondary hyperparathyroidism are common and contribute to age-related bone loss.
Other potential pathogenetic factors include declining levels of physical activity and intestinal calcium malabsorption.
Factors affecting peak bone mass →
- Genetic factors strongly influence bone mass, accounting for 70-80% of its variance.
- Sex hormone status
- Nutrition
Physical activity
Risk Factors: Endogenous
osteoporosis
- Advancing Age
- Female
- Caucasian or Asian race
- Fam history
Risk Factors: Exogenous
- Hypogonadism (either sex)
- Steroids
- Low BMI
- Previous or prevalent fragility fracture
Risk Factors for sustaining a fracture →
• Low bone mass • Personal or family history of fracture • Risk factors for falls: o Confusion disorders o Medications e.g. anxiolytics, sedatives, antihypertensives o Neuromuscular disease o Alcohol o Environmental factors e.g. poor lighting, uneven floor
DEXA
- Bone mineral density is measured at the femur and the lumbar spine – given T and Z scores.
- Minimal radiation
Indication for requesting a DEXA scan
• Low trauma/fragility fracture
• Oral glucocorticoids for 3 months or more or repeated courses of high dose steroids.
• Suggestion of osteopepenia on X-ray
• Predisposing medical conditions e.g. malabsorption, hypogonadism, and thyroid disease.
• Family history of osteoporosis or related fractures (especially maternal hip fracture)
• Low lifetime exposure to oestrogens e.g.
o Premature menopause (less than 45 years)
o Prolonged secondary amenorrhoea
o Post hysterectomy and oophorectomy
Z scores
• Gives an age-matched comparison of bone density
T scores
Gives a score to relate current bone density to predicted peak bone mass
→Less than -2.5 = osteoporosis (treat)
→Between -1.0 and- 2.5 = osteopenia (treat if history of low trauma fracture, or if taking glucocorticoids)
→ Greater than -1.0 = normal
Simple blood test effectiveness
for osteoporosis
• (Serum calcium, phosphate and alkaline phosphatase and urinary calcium0 are normal in primary osteoporosis.
Biochemical screen useful for in osteoprosis
- Renal or liver impairment
* Osteomalacia (raised alkaline phosphatase, low phosphate, raised level of parathyroid hormone and reduced vit D
Other screens
- Myeloma screen (plasma and urinary protein electrophoresis)
- Screen for coeliac disease (antigliadin antibodies)
Treatment → osteoporosis
Reduce risk of fracture
Diet →
Other Conservative measures →
Calcium and Vitamin D supplements →
Reduce risk of fracture
- Stopping bone loss
- Reducing bone turnover
- Increasing bone mass and strength
- Reducing fall risk
Diet →
- Should include at least 1000mg of calcium daily (1500 mg post menopause)
- 400-800 of Vitamin D
- Calcium salts – decrease in bone turnover
Other Conservative measures →
Pain Relief → combination of simple analgesics and use of TENS machine
Physio → improve mobility
Reducing fall risk →
Calcium and Vitamin D supplements →
Adjunctive therapy
Royal college of Physicians states that any patient over the age of 65 years beginning a course of glucocorticoid treatment for 3 months or over should
longer should be treated with a bisphosphonate ± calcium/vitamin D, without the need for a DEXA scan.
Bisphosphonates: Action
Adhere to hydroxyapatite and inhibit osteoclasts thereby suppressing bone resorption.
Strong affinity for calcium phosphate and act exclusively in calcified tissues.
Bisphosphonates: Most used example
Alendronate (weekly regimens)
Risedronate (weekly regimens)
Bisphosphonates: Newer agent
Bisphosphonate ibandronate (monthly)
Bisphosphonates: Intravenous options
Pamidronate
Ibandronate
Zoledronate (once a year)
Bisphosphonates: In combination
Vitamin D and calcium supplements
Bisphosphonates: Review of treatment
3-5 years reassement
Bisphosphonates: Side Effects
Upper Gi problems – oesophagitis
Poor oral availability (take without meals just water)
Raloxifene → Definition
Estrogen receptor modulators (SERMs) – exert estrogen-like effects on the skeleton, protect against breast cancer.
Raloxifene → With menopause
Increases the severity of hot flushes
Strontium → Effect
Stimulates osteoblasts activity and suppressing osteoclasts.
Strontium → Problem with strontium
Incorporated into the skeleton, leading to an artefactual increase in bone mineral density which makes it difficult to monitor response to treatment by repeat DXA scanning
Teriparatide → Definition
Recombinant parathyroid hormone (Teriparatide) for refractory osteoporosis
Teriparatide → Dosage
Daily subcutaneous injection 8 month course
Teriparatide → Confusing because
PTH stimulates osteoclasts, causing resorption of bone but evidence shows the daily pulses increases new bone formation.
Teriparatide → NICE guidelines
Treatment option in patients with severe osteoporosis (multiple vertebral fractures and low BMD)
Teriparatide →Evidence for treatment of
Back Pain
Other Management Options →
Activated vitamin D
Calcitriol
Alfacalcidol
Indication for activated Vitamin D
Young patients or women of childbearing age
Calcitonin →Use for and contraindications
Analgesic effects in patients with acute calcitonin treatment difficult to tolerate due to nausea and vomiting.
Vertebroplasty → Process
Percutaneous injection of bone cement directly into a fractured vertebral body
Vertebroplasty →Use
Painful vertebral fractures
