Bone remodelling pathologies

Frage	Antworten
List some factors that oppose bone resorption.	Vitamin D, calcium, calcitonin, bisphosphonates and oestrogen.
List some factors that oppose bone formation.	Immobilisation, ageing, sclerostin (SOST), and leptin/β-adrenergics.
List some factors that promote bone resorption.	Low calcium, low oestrogen, and immobilisation.
List some factors that promote bone formation.	Androgens, mechanical load, intermittent parathyroid hormones, β-blockers, bone morphological proteins (BMPs), and LRP5-Wnt signalling.
Which technique is used to determine bone mineral density by calcium levels?	Dual energy x-ray absorptiometry (DXA).
What is a T-score with regard to bone mineral density?	It is a measure of comparison of one person's bone mineral density (determined by dual energy x-ray absorptiometry) against that of a healthy 30 year old of the same sex and ethnicity.
What is a Z score with regard to bone mineral density?	It is a measure of comparison between one person's bone mineral density (as determined by dual energy x-ray absorptiometry) and that of an age-matched, sex-matched, ethnicity-matched individual.
Is a T score or a Z score more relevant in a postmenopausal woman?	A Z-score is more relevant because it addresses the natural pro-osteoclastic environment resulting from less oestrogen production.
When looking at the x-ray produced by dual energy x-ray absorptiometry to determine bone mineral density, what type of bone is one looking for the amount of?	Trabecular bone.
What is one's peak bone mass? When is it reached?	The accrual of bone mass in early life, usually reaching its maximum in one's second or third decade.
Which has the largest contribution to peak bone mass: genetics or the environment?	Genetics.
What is the most common bone disorder in post-menopausal women?	OSTEOPOROSIS, FOOL.
In osteoporosis there is excessive bone destruction. What is the imbalance in bone formation/resorption that results in this?	Osteoclastic activity is favoured over osteoblastic activity (partially as a result of less oestrogen stimulating the production of less osteoprotegerin to inhibit RANK/RANKL interaction), but osteoblasts are not in any way impaired.
Quantitatively, how is osteoporosis defined?	As a bone mineral density of 2.5(SD) below the peak bone mass of a healthy 30 year old of the same sex and ethnicity.
What complications is osteoporosis associated with?	An increased risk of fracture and a reduced healing efficiency.
Along with stimulating the production of osteoprotegerin (OPG) to limit osteoclastic activity, what else does oestrogen do to the same end?	It inhibits parathyroid hormone directly, to prevent it from maturing/activating osteoclasts.
What is primary osteoporosis?	That which does not result from another disease, but which develops in postmenopausal females, and in both males and females above the age of 75.
What is secondary osteoporosis?	That which occurs secondary to a chronic predisposing medical problem or disease, and which may occur at any age and affect males and females equally.
What three deficiencies are likely to be seen in primary osteoporosis?	Lack of oestrogen and low calcium and vitamin D.
How do low vitamin D levels contribute towards osteoporosis development?	Low vitamin D levels result in calcium deficiency and increased activity of the parathyroid glands to increase osteoclastic activity and calcium release.
How might chronic kidney failure lead to secondary osteoporosis?	If too much water is retained, the Ca2+ serum concentration could 'appear' lower overall, resulting in increased osteoclastic activity and bone breakdown to release more calcium.
How might Cushing's disease lead to secondary osteoporosis?	Cushing's disease is characterised by an increase in adrenocorticotropic hormone released from the anterior pituitary, often caused by a tumour. This binds to receptors in the adrenal glands and causes increased release of cortisol, a hormone involved in the mediation of long-term stress, which has many effects including reducing absorption and increasing excretion of Ca2+. This reduces the serum Ca2+ concentration and results in increased osteoclastic activity to compensate for it.
How might hyperparathyroidism result in secondary osteoporosis?	Hyperparathyroidism results in the increased release of parathyroid hormone, which matures/activates osteoclasts, resulting in increased osteoclastic activity.
How might hyperthyroidism result in secondary osteoporosis?	Increased thyroid hormones result in increased Ca2+ secretion, which decreases Ca2+ serum concentration, and results in increased osteoclastic activity to replace the Ca2+.
How might hypogonadism result in secondary osteoporosis?	Hypogonadism is diminished function of the gonads: testes and ovaries. In both men and women decreased oestrogen can lead to increased osteoclastic activity and a reduction in bone density. Reduced testosterone also results in reduced bone density, potentially because men convert it to oestrogen to increase bone density.
How might diabetes mellitus lead to secondary osteoporosis?	Type 1: is thought to be linked to osteoporosis as a result of decreased insulin and amylin, which may be involved in bone density and may explain why those with type 1 diabetes do not reach peak bone mass regularly. Type 2: hyperglycaemia results in more glucose being available for osteoclasts, and also results in hypercalciuria as as a result of both glycosuria and increased parathyroid hormone secretion. Further, complications such as obesity, impaired vision, and diabetic neuropathy may predispose to falls.
Osteoporosis is characterised by decreases in...?	Overall bone mass and density, cortical (compact bone) thickness, and size and number of trabeculae in cancellous (spongy bone).
Why do grannies get shorter as they age?	Primary osteoporosis type 1 occurs 'naturally', particularly in postmenopausal women. The increased osteoclastic activity that results from decreased oestrogen forms fewer, smaller trabeculae which allow the bone to be compacted together, shortening it and the granny!
What is kyphosis, or Dowager's hump? How is it formed?	Dowager's hump is a hunchback, a dorsal protrusion of the thoracic vertebrae resulting in a 'slouching' change in posture. In older people, it is formed as a result of compacted bone and vertebral fractures, along with loss of musculoskeletal integrity.
In osteoporosis, why are the hip and femoral bones at most risk of fracture?	They are predominately weight-bearing and so are under higher pressure and more likely to weaken - they are therefore easier to damage in a fall.
What is osteopenia?	A decrease in bone mineral density below peak bone mass, but not at an osteoporotic level. It is often a precursor to osteoporosis.
How might osteopenia be treated?	Ca2+ injections.
What is osteopetrosis?	A genetic dysfunction in osteoclasts results in increased bone mass density. However, this bone tends to be more brittle as irregular bone built as a result of injury cannot be broken down and replaced with regular tissue due to osteoclast dysfunction. This irregularity results in brittleness.
What is myeloma?	A cancer of the bone marrow (specifically the plasma cells) in which RANKL is overexpressed by osteoblasts resulting in increased osteoclastic activity.
In myeloma, what two factors result in increased osteoclastic activity?	Down regulation of OPG by stromal cells and over-expression of RANKL by tumour cells.
What type of lesion is most common in myeloma?	A painful, debilitating lytic lesion resulting from increased osteoclastic activity. Bone pain is very common.
The level of bone loss in which other condition is comparable with that of myeloma?	Osteopenia.
Why is myeloma so difficult to treat?	As a result of loss of regulation.

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