Calcium and Bone Disease: Pathology Final

Calcium

- Atomic weight of 4g/mol

- Divalent cation

- High in sea water

What form is calcium stored in in the bones

Tricalcium phosphate

Normal serum calcium

2.5 mmol/L

Lab testing for calcium

Normal total calcium is 2.5mmol/L, but only some of that is ionized and able to be biologically useful (1.2mmol/L)

Protein bound calcium

Not biologically available for membranes or bones, level not regulated

Serum calcium includes

Free calcium, protein bound calcium, and complex calcium (aka Ca citrate)

Why is calcium important in the body

- Stability of cell membranes

- Signaling

- Component in bone

- HIGHLY regulated in the body

Effect of high calcium in the cells

Causes phosphates in the cell membrane to stick together, the cell membrane is less fluid, less permeable, and less excitable

Effect of low calcium in cells

Less phosphates in the cell membrane sticking together leading to greater fluidity, permeability, and excitability

Physical tests that can be done to see low calcium

- Chovstek Sign

- Trousseau sign

Chovstrek sign

Rubbing the side of someone's face and seeing if they twitch, sign of low calcium

Trosseau sign

Hand cramping up, sign of low calcium

Primary purpose of bone

Calcium reservoir

Bone growth

- Bone is first a soft matrix

- Then gets vascularized

- Starts to calcify

- Growth happens from the epiphyseal plates (at the ends of bone, not mineralized)

Growth continues to happen until fusion of the epiphyseal growth plates

Fusion of epiphyseal growth plates

After puberty, you stop growing

Damage of an epiphyseal growth plate

Damage before fusion can lead to that limb not being able to grow properly

Average rate of increase in height (cm/year)

Height growing fast from birth, but then levels off, then increases again at a growth spurt at puberty, but then levels off again after puberty and you eventually lose height

Velocity of growth highest when you are younger and during puberty

Alkaline phosphatase

Marker of bone turnover, highest before the epiphyseal plate fusion but after that becomes lower unless a condition is causing abnormalities in ALP (ex. fractures, etc)

Bone remodelling

Process done by osteoblasts (build bone) and osteoclasts (break down bone)

Every month, we dissolve 1% of our skeleton and build back 0.9% of it, meaning each year we lose 1% of our skeleton

Bone formation lags behind bone absorption

Cortical bone

Dense part of bone that prevents bending

Trabecular bone

Less dense part of bone that prevents crushing

3 hormones that regulate ionized calcium in the body

- Active vitamin D3 (calcitriol)

- Parathyroid hormone

- Calcitonin

Action of parathyroid hormone

Activated when serum calcium is low.

Causes increased activity of osteoclasts which cause bone resorption, cause an increase in active vitamin D3, and causes increased renal absorption of calcium

Action of active vitamin D

Active when serum calcium is low

Cause increase intestinal absorption of calcium

Action of calcitonin

Active when serum calcium is high

Cause increase in bone formation

What happens when calcium is low and parathyroid hormone is low

Primary hypoparathyroidism

What happens when calcium is relatively normal but parathyroid is high

Kidney disease, which cannot make vitamin D to suppress PTH

What happens when calcium is very high but parathyroid hormone is low

Bone metastasis could be happening where the calcium in the bones is getting chewed away leading to very high serum calcium

What happens when calcium is high and parathyroid is high

Primary hyperparathyroid

What happens when you consume calcium (1000mg)

800mg goes out in the stool, 200mg is absorbed and is in equilibrium with bone before it is renally excereted

What happens when you consume calcium (less than the required amount) and do not have vitamin D

Body will use the calcium stores from the bone to normalize serum calcium, leading to low bone density

What happens when you consume calcium and vitamin D

Vitamin D enhances the absorption of calcium

Bone as a biomaterial

Self-engineered material that realigns based on the stress that is imposed on it, dynamic tissue

Z-scores for osteoporosis

Shows your value in comparison to people of the same age group

T-scores for osteoporosis

Compares your value with a person who has ideal bone density (under 35 years old)

Osteoporosis diagnosis

T score of less than -2.5

As people age, their bone density gets less but the reference for osteoporosis stays the same, meaning lots of people get diagnosed with osteoporosis as they get older

When you are over 70, what is a better predictor of life expectancy than blood pressure/cholesterol

Bone density

Survival with and without hip fracture

Survival rates decrease after a hip fracture for both men and women

Hip fractures as a predictor of life expectancy, vertebral or other fractures also decrease life expectancy but not as much as hip fractures

Risk factors for hip fractures

- Low BMD

- Low calcium/vitamin D intake

- Older adult

- Perceived health

- Low BMI

- Low exercise

Bone turnover lab testing

Expensive and not often done, little clinical importance

Osteoporosis treatment and compliance

Bisphosphonates are only working to increase BMD and decrease risk of fractures if people are actually filling and taking their medications as prescribed

No osteoporosis therapy is effective without _______________________

Calcium, vitamin D

All RTCs have been done in the presence of calcium and vitamin D as well as the drug

What effect would an antiresorptive drug (bisphosphonate) have on serum alkaline phosphatase

Lower

Calcium nutrition advice for patients

RDA around 1000mg/day, if you need to figure out how much calcium a patient can have you can use calcium calculators

If you are consuming _____mg of calcium per day there is no need for a supplement

800mg