Endocrine and metabolic bone disorders Flashcards
Briefly describe the composition of bone
Bone is generally comprised of a calcified matrix called osteoid, and three
types of bone cell, the osteoblasts, osteoclasts and osteocytes which continually synthesise and remodel the matrix.
- The organic part of the osteoid is almost entirely made of type 1 collagen, with the remaining 5% called ground substance being composed of proteoglycans.
- The complex hydroxyapatite crystals, which are comprised of hydrated calcium phosphate salts, form along
the collagen fibres. This hydroxyapatite provides the long-term storage
form of calcium and phosphate.
Differentiate between woven and lamellar bone
Lamellar bone can be of the cortical (hard) or trabecular (spongy) type = has a regular parallel alignment of collagen (in alternating orientations) and is mechanically strong
Woven bone = disorganised collagen fibrils, weaker
Why is it rickets in children and osteomalacia in adults?
RICKETS:
- affects cartilage of epiphysial growth plates and bone
OSTEOMALACIA:
- after epiphyseal closure, affects bone
Outline the consequences impaired regulation of serum calcium and phosphate due to renal failure
Because the kidneys are the site of the enzyme that hydroxylates 25
hydroxycholecalciferol to produce calcitriol, renal impairment can result in
a deficiency of this enzyme. This will result in low levels of calcitriol, which in turn will cause secondary hyperparathyroidism. The renal impairment in addition means that there is a decreased excretion of phosphate, so that
a low blood level of calcium with a high level of phosphate can result. The
consequent effects of very high levels of PTH on the bone in this situation
mean that significant loss of bone can result => osteitis fibrosa cystica
What can an elevated plasma phosphate concentration lead to?
vascular calcification
What does Osteitis fibrosa cystica look like on x ray? Describe its treatment
Presents as ‘Brown tumours’ = radiolucent bone lesions
- Treat the hyperphosphataemia with low phosphate diet and phosphate binders to reduce GI phosphate absorption
- Give Alphacalcidol (i.e. calcitriol analogues)
- Parathyroidectomy in tertiary hyperparathyroidism (hypercalcaemia)
Characterise osteoporosis.
- Loss of bony trabeculae
- Reduced bone mass
- Weaker bone predisposed to fracture after minimal trauma
- A feature of normal ageing
How is osteoporosis diagnosed?
DEXA scan - femoral neck and lumbar spine; Mineral (calcium) content of bone measured.
Bone mineral density (BMD) > 2.5 standard deviations below the average value for young healthy adults (usually referred to as a T-score of -2.5 or lower)
BMD predicts future fracture risk
Distinguish between osteoporosis and osteomalacia
OSTEOMALACIA:
- Vitamin 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
State the pre-disposing conditions for osteoporosis
- Postmenopausal oestrogen deficiency
- Age-related deficiency in bone homeostasis (men and women) e.g. osteoblast senescence
- Hypogonadism in young women and in men
- Endocrine conditions e.g. Cushing’s syndrome, Hyperthyroidism, Primary hyperparathyroidism
- Iatrogenic e.g. prolonged use of glucocorticoids, heparin
List the treatment options for osteoporosis
- Oestrogen/Selective Oestrogen Receptor Modulators
- Bisphosphonates (1st line)
- Denosumab (2nd line)
- Teriparatide (3rd line)
When treating post-menopausal osteoporosis with pharmacological doses of oestrogen, what are the considerations/limitations?
Women with an intact uterus need additional progestogen to prevent endometrial hyperplasia/cancer
Use limited largely due to concerns regarding:
- Increased risk of breast cancer
- Venous thromboembolism
What do bisphosphonates do?
- Bind avidly to hydroxyapatite and ingested by osteoclasts => impaired ability of osteoclasts to reabsorb bone
- Decrease osteoclast progenitor development and recruitment
- Promote osteoclast apoptosis (programmed cell death)
Net result = reduced bone turnover
What are the clinical uses of bisphosphonates, other than ostroporosis?
Malignancy:
- associated hypercalcaemia
- reduce bone pain from metastases
Paget’s disease
- reduce bony pain
Severe hypercalcaemic emergency (i.v. initially but +++ re-hydration first)
How are bisphosphonates administered? Where do they accumulate and for how long?
Orally active but poorly absorbed so take on an empty stomach (food, especially milk, reduces drug absorption generally)
Accumulates at site of bone mineralisation and remains part of bone until it is resorbed (after months or years)
