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Physiology & Science: Ageing > Hormones, the skeleton and HRT > Flashcards

Hormones, the skeleton and HRT Flashcards

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1
Q

Which hormone is replaced in hormone replacement therapy?

A

Oestrogen

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2
Q

Name some systemic hormones with skeletal effects

A
  • Oestrogen
  • Parathyroid hormone (PTH)
  • Vitamin D
  • Calcitonin
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3
Q

What is the macrostructure of bone?

A
  • Cortical (compact) bone - around outside of bone and composes main part of shaft
  • Trabecular (spongy) bone - tends to be in head of bone
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4
Q

What are osteoblasts?

A
  • Differentiate from mesenchymal stem cells
  • Bone forming cells - lay down osteoid + promote mineralisation of osteoid
  • Life cycle determined by control of differentiation and apoptosis
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5
Q

What are osteoclasts?

A
  • Derived from haematopoietic stem cells
  • Resorption of bone - secrete acid to dissolve + release mineral, enzymes to degrade osteoid/matrix
  • Life cycle determined by control of differentiation + apoptosis
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6
Q

What are osteocytes?

A
  • Terminally differentiated, post-mitotic osteoblasts
  • Entombed within lacuae in bone matrix
  • Communicate with each other + bone surface via dendrites which run along canaliculi
  • Lacunar-canalicular network
  • May live for decades
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7
Q

What actually is the function of osteocytes?

A
  • Regulate bone remodelling in response to mechanical + endocrine stimuli
  • Function as endocrine cells
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8
Q

What is the lacunar-canalicular network?

A
  • Lacunar = holes (where cells are)
  • Canalicular = networks (between cells)
  • Allows communication between osteocytes and from osteocytes to surface cells + systemic circulation
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9
Q

Control of remodelling: What are factors favouring resorption?

A
  • Unloading
  • Eg. bedrest, zero-gravity
  • Ie. lack of mechanical stress
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10
Q

Control of remodelling: What are factors favouring formation?

A
  • Load bearing exercise
  • Osteocytes involved in sensing mechanical stress for this
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11
Q

Bone turnover serves homeostasis of serum calcium and phosphate, in conjunction with which hormones?

A
  • PTH
  • Vit D (calcitriol)
  • Calcitonin
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12
Q

What is the role of PTH (parathyroid hormone)?

A
  • Control plasma calcium (2.2-2.6 mmol/L)
  • Released in response to decreased Ca
  • Stimulates 1-a hydroxylase -> forms active vitamin D in kidney
  • Increases Ca reabsorption in kidney
  • Promotes bone remodelling (anabolic + catabolic)
  • Prevents osteoblast + osteocyte apoptosis
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13
Q

What are the actions of Vitamin D?

A
  • Increases Ca absorption from gut
  • Promotes differentiation of osteoclast + osteoblast lineages
  • Inhibits PTH release
  • Inhibits 1-alpha hydroxylase
  • Necessary for bone mineralisation

Vitamin D is synergistic with PTH

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14
Q

What are actions of calcitonin?

A
  • Released from C-cells of thyroid gland
  • Neg feedback reg of serum Ca -> released in response to inc Ca
  • Lowers serum calcium
  • Importance in human Ca homeostasis is doubtful
  • Inhibits osteoclast function (preventing resorption -> lowering serum Ca)
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15
Q

How does oestrogen act on osteoblasts and osteoclasts?

A
  • Oestrogen receptors present on both osteoclasts and osteoblasts
  • Regulates life cycle of them both
  • Osteoclasts -> promote apoptosis -> shorten life cycle
  • Osteoblasts -> protect from apoptosis -> lengthen life cycle
  • Indirectly inhibit osteoclast differentation
  • May be necessary for new bone formation in response to mech stress
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16
Q

What is RANK?

A
  • Receptor activator of nuclear factor kappa-B
  • It’s a surface receptor on pre-osteoclasts, when activated it stimulates osteoclast differentiation
17
Q

What is RANK-ligand?

A
  • RANK ligand prod by pre-osteoblasts, osteoblasts + osteocytes
  • Binds to RANK (receptor) + stimulates osteoclast differentation
18
Q

What is OPG (osteoprotogerin)?

A
  • Decoy receptor prod by osteocytes
  • Binds to RANK-L, preventing activation of RANK
  • Preventing osteoclast differentation

Ratio between RANK ligand and OPG is critical in controlling rate of bone resorption

19
Q

What is sclerostin?

A
  • Produced by osteocytes
  • Inhibits osteoblast differentiation
  • Essential negative feedback on bone formation
  • Absence -> excessive bone formation
  • It’s a brake on bone formation + mechanical stress can take this brake off
20
Q

What is osteoporosis?

A
  • Loss of bone mass
  • Affects cortical and trabecular bone
21
Q

What is osteomalacia?

A

Loss of bone mineralization

22
Q

What are the causes for osteoporosis?

A
  • Endocrine
  • Malignancy
  • Drug-induced
  • Renal disease
  • Nutritional
23
Q

What are the endocrine causes of osteoporosis?

A
  • Hypogonadism - notably any cause of ostrogen deficiency
  • XS glucocorticoids - endogenous or exogenous
  • Hyperparathyroidism
  • Hyperthyroidism
24
Q

How do you diagnose osteoporosis?

A
  • Measurement of bone mineral density (BMD)
  • By DEXA scan (dual-energy x-ray absorptiometry)
  • Result = T score (# of SDs below average for young adult at peak bone density)
  • Z score = matched to age and/or group
25
Q

What is the T score diagnosis for osteoporosis?

A
26
Q

Can oestrogen be a given as treatment for osteoporosis?

A

Yes - Effects well established but safety of long term treatment has been questioned

27
Q

What is the usual first line treatment for osteoporosis?

A
  • Bisphosphonates
  • Inhibit function of osteoclasts
  • Risedronate, alendronate
28
Q

PTH analogues can be used to treat osteoporosis, what is important about this?

A
  • PTH can be anabolic and catabolic
  • Must be dose-time dependent therapy
29
Q

What is the name of the (drug) antibody used against RANK ligand, in order to treat osteoporosis?

A

Denosumab - for postmenopausal as well

30
Q

What are lifestyle treatments for osteoporosis?

A
  • Adequate calcium + vitamin D intake
  • Appropriate exercise
31
Q

What are clinical features of the menopause?

A
  • Most common early manifestation: vasomotor symptoms (hot flushes)
  • Later: accelerated bone loss, osteoporosis
32
Q

With oestrogen and progesterone therapy (HRT), how is the relative risk of getting breast cancer 27%?

A
  • Placebo relative risk = 0.30
  • oestrogen + progesterone relative risk = 0.38
  • 38-30 = 8
  • 8/30 x 100 = 27%
  • Therefore 27% increase in terms of relative risk
  • AKA 1.27 more times likely to develop breast cancer if you go for HRT
33
Q

What is the NICE guidance for HRT?

A
  • HRT most effective treatment for relief of vasomotor symptoms although other options are available
  • For most symptomatic, menopausal women, the benefits of HRT outweigh the risks
  • Inc in risk of breast cancer exp with some HRT preparations disappears once HRT is stopped

Physiology & Science: Ageing (13 decks)

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