Calcium and Phosphate Metabolism Flashcards
- Bone turnover/remodelling serves as a short term service of calcium and phosphate homeostasis, what is this also in conjunction with?
- Parathyroid hormone (PTH)
- Vitamin D (1,25-dihydroxy D3)
- Calcitonin
FGF-23
- What % of body calcium is in the bone?
- Where is the remaining %
99%
Remaining 1% is mainly intracellular
- What percentage and amount of calcium is extracellular
- Is this bound (to albumin) or free?
Tiny (<0.1%) extracellular fraction
Plasma extracellular Ca is 2.2-2.6 mmol/L
Around half is free, half is bound
- What % of the bodies phosphorus is found in bone?
- What is the remainder of phosphorus?
85%
Remainder is mainly intracellular
- What levels fluctuate more, calcium and phosphate?
Phosphate
- What are the clinical features of hypercalcaemia?
Depression, fatigue, anorexia, nausea, vomiting,
Abdominal pain, constipation
Renal calcification (kidney stones)
Bone pain
“painful bones, renal stones, abdominal groans, and psychic moans,”
- What are some severe clinical features of hypercalcaemia?
cardiac arrhythmias, cardiac arrest
- What are the most common causes of hypercalcaemia?
In ambulatory patients: primary hyperparathyroidism
In hospitalised patients: malignancy
- What are the less common causes of hypercalcaemia?
Hyperthyroidism
Excessive intake of vitamin D
- What is Alkaline phosphatase?
. Enzyme found in liver, bone and many other tissues. In presence of bone disease may be elevated due to increased bone turnover.
- What should the levels of plasma:
-Calcium
-Phosphate
-Alkaline phosphatase
-Creatinine
-PTH
be in a normal situation (ie the serum biochemistry)
- Serum calcium - modest to marked increase
- Serum phosphate (decreased reabsorption, increased excretion by PTH) - low or low normal.
- Serum alkaline phosphatase raised in ~ 20% of cases due to increased bone turnover etc.
- Serum creatinine may be elevated in longstanding disease (kidney damage)
- Serum PTH concentration should be interpreted in relation to calcium.
- If PTH is inappropriately normal and calcium levels are elevated –> What should you investigate for?
PTH inappropriately normal because they should be low if calcium is high
Investigate for hyperparathyroidism
- Case study:
A 52 year old woman was investigated for
suspected kidney stones.
Serum investigations:
Total calcium 2.82 mmol/L (2.20 - 2.52) Phosphate 0.69 mmol/L (0.75 - 1.50) Albumin 42 g/L (35 - 48) Alkaline phosphatase 135 U/L (30 - 100) PTH 7.3 pmol/L (1 - 6.9) Creatinine 118 mol/L (60 - 110)
Explain these results
Hypercalcaemia (kidney stones) due to hyperparathyroidism.
Calcium HIGH
(PTH HIGH)
(Creatinine HIGH)
- What is the most common cause of hypercalcaemia in hospitalised patients
(Hypercalcaemia of malignancy)
o Humoral, e.g., lung carcinoma secreting PTH related Peptide which acts on PTH receptors.
o Metastatic tumour (release cytokines that promote osteoclast differentiation for bone resorption).
o Haematological: myeloma (tumour originating in the haematopoietic stem cell lineage).
15.What is the most common cause of hypocalcaemia?
Vitamin D deficiency Renal failure
- What is a less common cause of hypocalcaemia?
Hypoparathyroidism
- What is Rickets?
in children, failure of bone mineralisation of cartilaginous growth plates and disordered cartilage formation
- What is osteomalacia?
- in adults, impaired bone mineralisation of osteoid due to combination of low dietary intake and lack of sunlight exposure.
- Who is most at risk of osteomalacia?
: elderly in nursing homes and not taking supplements or breast-fed babies who are kept out of sunlight.
- What are some features of osteomalacia?
•Diffuse bone pain, waddling gait (way of walking caused by pelvic muscle weakness), muscle weakness, stress fractures (on x-rays).
- What is the serum biochemistry of osteomalacia?
Low/normal calcium, Hypophosphataemia (should increase)
Raised alkaline phosphatase, Secondary hyperparathyroidism
- What is osteoporosis?
health condition that weakens bones, making them fragile and more likely to break
- What are some features of osteoporosis?
oLoss of bone mass: endocrine, malignancy, drug-induced, renal disease, nutritional.
o Loss of bone density
increased fracture risk, increase in bone resorption over formation.
- Because osteoporosis is usually asymptomatic , how is one usually diagnosed with it?
a fragility (minor falls break bones) fracture in wrists/femur or vertebral fractures.
- What are some endocrine associated causes of osteoporosis?
- Hypogonadism: especially any cause of oestrogen deficiency
* Excess endogenous or exogenous glucocorticoids, Hyperparathyroidism or Hyperthyroidism.
- What is the difference between a T and Z score?
The T-score is a comparison of a person’s bone density with that of a healthy 30-year-old of the same sex.
Its a number (SDs)
The Z-score is a comparison of a person’s bone density with that of an average person of the same age and sex
- How do we diagnose osteoporosis?
Measurement of bone mineral density (BMD)
Dual-energy X-ray absorptiometry (DEXA or DXA scan)
- In terms of T score, what would be seen in:
-Normal
-Osteopenia
-Osteoporosis
-Severe Osteoporosis
??
Normal = T-score of -1 or above
Osteopenia (naturally, with age) = T-score lower than -1 and greater than -2.5
Osteoporosis =T-score of -2.5 or lower
Severe osteoporosis= T-score of -2.5 or lower, and presence of at least one fragility fracture
- When does bone density peak?
•Bone density peaks at 25-30 years old after which it declines, the decline is accelerated by menopause.
- How is bone mass for men different to bone mass for women
higher peak of bone density due to larger mass and no accelerated decline due to no menopause.
- Does the risk of osteoporosis increase with age?
Yes
- What is the treatment for osteoporosis?
- Postmenopausal: HRT (hormone replacement therapy) – effects well established but safety of long term treatment has been questioned.
- Bisphosphonates e.g. risedronate, alendronate – inhibit function of osteoclasts.
- PTH analogues: intermittent dose and time-dependent favour remodelling.
- Denosumab – antibody against RANK ligand (reduced osteoclast differentiation so reduced resorption).
- Romosozumab (approved 2019, Japan, USA, EU). - antibody against sclerostin protein so increased osteoblast differentiation.
- Ensure adequate calcium and vit D intake, appropriate exercise.
- What is the brief history of HRT?
* I dont know if we need to know this guys:) *
- US approves Premarin (conjugated equine oestrogen: PREgnant MAre’s urINe) treatment of hot flushes
- Feminine Forever by gynaecologist Robert Wilson promoting HRT as lifestyle choice
- 1970s. Strong association between oestrogen therapy and endometrial cancer so HRT (oestrogen only) use declines.
- 1980s. Combination HRT products (progestins added to counter proliferative effects of unopposed oestrogen on endometrium) use rises again (oestrogen-progesterone).
- Preventative effect on BMD, osteoporosis and other claimed benefits: e.g., CV protection – evidence from experimental literature, but no large RCTs (randomised control trials).
- HRT use peaks late 1990s (15 M women in USA)
34 . Which randomised controlled trial took place for HRT?
o Women’s Health Initiative (WHI) in USA,, Million Women Study in UK, 2002 preliminary results from WHI published
o No CV protective effects (possibly the reverse).
o Claimed significantly increased breast cancer risk followed by years of controversy and debate
35 . What were the Overall Effects from WHI: % of women per year (all ages):
- Fracture risks reduced massively with hormone replacement therapy.
- Cancer risk reduced with just oestrogen but increased with oestrogen-progesterone combined therapy.
- What is relative risk versus absolute risk?
If something you do triples your risk, then your relative risk increases 300%. Absolute risk is the size of your own risk
(Media quotes only relative risk without absolute risk–> Can be misleading)
- What were further analysis of the WHI results?
- How were the guidelines for HRT modified because of this
• The original WHI participants were older, post-menopausal women (mean age of 64 and 10 years post-menopause).
• Separate analysis of <10 or >10 yrs post-menopause suggested risks were reduced in earlier group.
• Guidelines for HRT modified:
o Short-term therapy (3-5 years) for treating vasomotor (blood pressure) symptoms.
o Lowest effective dose is to be used and long term use is not recommended.
38 . What do the NICE guidelines for HRT in 2015 state?
- > HRT is the most effective treatment for relief of vasomotor symptoms although other options, including non-pharmacological ones are available
- > For most symptomatic. menopausal women, the benefits of HRT outweigh the risks
- Give an overview of the signal networks in bone remodelling?
- Osteocytes detect small/minor stress fractures and cause osteoclast recruitment, proliferation, differentiation.
- Activated osteoclasts result in bone resorption (digestion and release of minerals) before they die by apoptosis.
- Osteoblasts are recruited to the area of resorbed bone and they replace it with osteoid which is then mineralised.
