Endocrine and Metabolic Bone Disorders Flashcards
Role of osteoblasts?
bone formation, make bone, help deposit calcium
Role of osteoclasts?
dissolve bone and liberate calcium
Where is RANKL found
osteoblast surface
- RANKL binds to X to stimulate YYYY
X - RANK receptors
YYYY - osteoclast formation and activity
- Osteoblasts express receptors for X and Y
PTH and CALCITRIOL
Where are RANK receptors found
Osteoclast precursors
2 types of bone?
Cortical bone: hard bone on the outside
Trabecular bone: spongy, “trabecular” bone on the inside.
What is cortical bone
hard bone on the outside
What is Trabecular bone
spongy, “trabecular” bone on the inside.
What is spongy bone on the inside known as
Trabecular bone
What is hard bone on the outside known as
cortical bone
newly formed bone matrix is called …
osteoid
Osteoid is …
newly formed bone matrix
Vit D deficiency in children causes?
RICKETS
What part of the bone does a Vit D deficiency affect in children
Affects cartilage of epiphyseal growth plates and bone
Vit D deficiency in adults causes?
OSTEOMALACIA
What part of the bone does a Vit D deficiency affect in adults
after epiphyseal close, affects bone
Affects of rickets? (3)
Skeletal abnormalities and pain, growth retardation, increased fracture risk
Affects of osteomalacia? (3)
Skeletal pain, increased fracture risk, proximal myopathy
What is a looser zone
areas that have lost the mineralisation of the bone due to vit D deficiency
What is PRIMARY HYPERPARATHYROIDISM
A parathyroid adenoma leads to a busy parathyroid gland meaning serum PTH goes up - autonomous PTH secretion
What is secondary HYPERPARATHYROIDISM
a physiologically appropriate high PTH level and a low/normal calcium (because of e.g. renal failure, vitamin D deficiency)
What is tertiary HYPERPARATHYROIDISM
Chronically low plasma calcium which can happen because of renal failure, the overworked parathyroid glands can become autonomous without a cancer being involved
How does decreased renal function lead to vascular calcification (3 steps)
lower renal function, so less calcitriol, so more PTH and so more phosphate absorbed in the intestines and so increased serum phosphate which contributes to vascular calcification
How does decreased renal function lead to osteitis fibres cystica (like 8/9 steps)
decrease in renal function will lead to a decrease in the production of calcitriol (because of a lack of 1alpha hydroxylase)
decreased calcitriol leads to decrease in calcium absorption from the intestines leading to hypocalcaemia
hypocalcaemia will stimulate PTH release
PTH will break down bone matrix
breaking down of bone matrix will lead to osteoporosis
Due to the hypocalcaemia you get a decrease in bone mineralisation
combination of the increased bone resorption and decreased bone mineralisation will lead to osteitis fibrosa cystica a
Osteitis fibrosa cystica appears on X rays as ….
Brown tumours
TREATMENT OF OSTEITIS FIBROSA CYSTICA (3)
- Treat HYPERPHOSPHATAEMIA with low phosphate diet, and phosphate binders which reduce GI phosphate absorption
- ALPHACALCIDOL (i.e. calcitriol analogues)
- PARATHYROIDECTOMY in tertiary hyperparathyroidism indicated by hypercalcaemia and/or hyperparathyroid bone disease
Osteoporosis is characterised by: (3)
- Loss of bony trabeculae
- Reduced bone mass
- ## Weaker bone (predisposed to fractures after minimal trauma)
Osteoporosis is more common in… because…
More common in post-menopausal women (loss of oestrogen’s positive effect on bone)
OSTEOPOROSIS is defined as :
Bone mineral density (BMD) 2.5 SDs below the average value for young healthy adults
Bone mineral density predicts…
BMD predicts fracture risk
What measures Bone mineral density
Dual Energy X-ray Absorptiometry (DEXA)
Dual Energy X-ray Absorptiometry (DEXA) measures …
- Mineral (calcium) content of bone measured
More mineral = greater bone density
Difference between osteomalacia and osteoporosis?
OSTEOMALACIA:
- Vit D deficiency (adults) causing inadequately mineralised bone
- Serum biochemistry abnormal (low 25(OH) vit D, low Ca2+, high PTH (secondary hyperparathyroidism)
OSTEOPOROSIS:
- Bone reabsorption exceeds formation
- Decreased bone mass
- Serum biochemistry normal
- Diagnosis via DEXA scan
Similarities between osteomalacia and osteoporosis?
BOTH PREDISPOSE TO FRACTURE
Both have weak bones
PREDISPOSING CONDITIONS FOR OSTEOPOROSIS: (5)
Postmenopausal oestrogen deficiency
- Age-related deficiency in bone homeostasis e.g. osteoblast senescence
- Hypogonadism in young men/women
- Endocrine conditions
- Iatrogenic
What are the iatrogenic causes of Osteoporosis (2)
Prolonged use of glucocorticoids
Heparin
What are the Endocrine causes of Osteoporosis (3)
Cushing’s
Hyperthyroidism
Primary hyperparathyroidism
TREATMENT OPTIONS FOR OSTEOPOROSIS: (4)
- Oestrogen/Selective Oestrogen Receptor Modulators (SERMS)
- Bisphosphonates
- Denosumab
- Teriparatide
Use of E limited due to concerns over … (2)
breast cancer and venous thromboembolism
SERMS used in osteoporosis?
TAMOXIFEN and RALOXIFENE
Of TAMOXIFEN and RALOXIFENE, which is the better SERM
Raloxifene as it has Oestrogenic activity in bone, but anti-oestrogenic at breast and uterus
whereas tamoxifen is oestrogenic in uterus (endometrial proliferation)
How do BISPHOSPHONATES work (3)
Bind avidly to hydroxyapatite and ingested by osteoclasts- impair ability of osteoclasts to reabsorb bone
Decrease osteoclast progenitor development and recruitment
Promote osteoclast apoptosis
First line treatment for osteoporosis?
Bisphosphonates
What are bisphosphonates used for and what do they do (4)
Osteoporosis (1st line)
Malignancy Associated hypercalcaemia, reduce bone pain from metastases
Paget’s disease- reduce bony pain
Severe hypercalcaemic emergency- I.V. initially (rehydrate first)
RoA and absorption of busphosphonates? 1/2 life?
- Orally active but poorly absorbed; take on an empty stomach as food reduces drug absorption
- Accumulates at site of bone mineralisation and remains part of bone until it’s resorbed (months/years)
Unwanted effects of bisphosphonates?
Oesophagitis
Osteonecrosis of the jaw-
Atypical fractures
What is DENOSUMAB
- Human monoclonal antibody
What does DENOSUMAB do
- Binds RANKL, inhibiting osteoclast formation and activity
- Hence, inhibits osteoclast-mediated bone resorption
2nd line treatment for osteoporosis?
Denosumab
What does TERIPARATIDE do
- Increases bone formation and resorption, but formation outweighs resorption
Whats teriparatide
- Recombinant PTH fragment- amino-terminal 34 amino acids of native PTH
Big con of teriparatide?
- Expensive
What is PAGET’S DISEASE (OF BONE) and whats it caused by
Accelerated, localised but disorganised bone remodelling
Excessive bone resorption (osteoclastic overactivity) followed by a compensatory increase in bone formation (osteoblasts)
PAGET’S DISEASE (OF BONE) effect on bone?
BONE FRAILTY, HYPERTROPHY AND DEFORMITY
PAGET’S DISEASE (OF BONE) is characterised by…
by abnormal, large osteoclasts- excessive in number
Where do you woven bone
Pagets disease
CLINICAL FEATURES of Pagets disease? (8)
- Skull, thoracolumbar spine, pelvis, femur and tibia most commonly affected
- Arthritis
- Fracture
- Pain
- Bone deformity
- Increased vascularity (warmth over affected bone)
- Deafness (cochlear involvement)
- Radiculopathy (pinched nerve)- due to nerve compression
Pagets disease plasma levels of:
Ca
Alkaline phosphatase
Ca - normal
Alkaline phosphatase - increase
Treatment for Pagets disease? (2)
- BISPHOSPHONATES- reduce bony pain and decrease activity
2. Simple analgesia
