Calcium, Vitamin D, and Bone Health Essentials for Undergrads This is a non-exhaustive overview of key players in bone health, aimed at undergraduate students. Please note: This information is for educational purposes only and does not constitute medical advice. The authors do not guarantee the accuracy or suitability of this information for clinical use. Always consult a healthcare professional for personalized guidance. Calcium: Crucial mineral for building and maintaining strong bones. Primary source: Diet (dairy, leafy greens, fortified foods). Deficiencies: Rickets in children, osteoporosis in adults. Supplements: Used to address deficiencies, but overuse can be harmful. Vitamin D: Fat-soluble vitamin crucial for calcium absorption. Synthesized in skin via sun exposure, obtained from diet (oily fish, eggs). Deficiencies: Rickets, osteomalacia, osteoporosis. Supplements: Often recommended, especially in low sun exposure conditions. Bone Resorption and Formation: Constant process of bone breakdown (osteoclasts) and rebuilding (osteoblasts). Calcium and vitamin D play key roles in supporting this process. Medications for Bone Health (brief mention): Bisphosphonates: Inhibit bone resorption, first-line for osteoporosis. Teriparatide: Stimulates bone formation, used for severe cases. Denosumab: Targets bone resorption, alternative for postmenopausal osteoporosis. Calcitonin: Lowers blood calcium in emergencies, not for long-term use. Raloxifene: Protects bone and reduces fracture risk in women, similar to estrogen.

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Pharmacology of drugs used in calcium disorder
Calcium, the most abundant mineral in our body, is essential for normal bones and teeth, muscle
contraction, nerve transmission, and blood clotting. Phosphorus: A key component of DNA,
RNA, and ATP, crucial for bone health, cell signaling, and acid-base balance. Magnesium:
Plays a role in many enzymatic reactions, vital for muscle function, energy production, and
blood pressure regulation. The following focuses on diseases associated with the dysregulation
of calcium, and brief pharmacology of commonly used drugs.
Hypocalcemia:
 Symptoms: Muscle cramps, tingling, fatigue, seizures, irregular heartbeat.
 Causes: Vitamin D deficiency, kidney disease, thyroid problems, malnutrition, certain
medications.
 Management depends on severity: Vitamin D (cholecalciferol, ergocalciferol), calcitriol,
and calcium supplements (carbonate, citrate, gluconate).
 In severe cases parenteral calcium salts e.g. Calcium gluconate is recommended, avoid
fast infusion.
Hypercalcemia :
 Symptoms: Nausea, vomiting, constipation, kidney stones, fatigue, bone pain.
 Causes: Primary hyperparathyroidism, excess vitamin D intake, certain cancers,
medications (diuretics, lithium).
 Drugs (Classes): hydration therapy, parenteral Calcitonin, parenteral bisphosphonates,
and glucocorticoids,.
 In special cases such as cancer in the bone-specific drugs are considered e.g
Or in case of hyperparathyroidism Cinacalcet (calcimimetic) can be considred
Osteoporosis:
 Management depends on severity, Age, gender , risk for spine fractor , medication
history , postmenopausal women,.
 Drugs (Classes): calcium suplimint, Bisphosphonates, Vitamin D, denosumab,
raloxifene, teriparatide , calcitonin
 Note that some drugs have off-label uses ( beyond the scope of this lecture )

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Calcium gluconate and other calcium salts
Primarily used to treat hypocalcemia, parenteral use in case of severe emergency hypocalcemia.
Off-label uses include managing hyperkalemia., slow infusion is crucial to ensure safe use.:
Vitamin D
 Fat-soluble vitamin synthesized in skin or obtained from diet (D2, D3).
 Activated in liver to 1, (OH)2D then in kidney to 1,25(OH)2D, the active form.
(calcitriol )
 Increases intestinal calcium and phosphate absorption, bone resorption, and decreases
renal excretion of calcium.
 deficiency causes rickets in children or osteomalacia and osteoporosis in adults
 Inhibits PTH secretion directly and indirectly by raising serum calcium.
 It may be indicated for Psoriasis (topical) and off-label for other conditions.
Adverse Effects of Vitamin D:
 Chronic overdose may cause hypercalcemia, hyperphosphatemia, and hypercalciuria.
Specific Conditions and Considerations*****
 Individuals with severe liver or kidney impairment may require 1,25(OH)2D (calcitriol)
due to compromised activation of Vit D3.
Vit D is stored in the body for several weeks, allowing for single large doses, but you have to
avoid overdose
Teriparatide:
 It is a recombinant form of human parathyroid hormone (PTH).
 Indicated for certain cases of severe osteoporosis, T-score ≤ -2.5 with at least one
fragility fracture) individuals with a high risk of fracture, postmenopausal women, and
men with primary or hypogonadal osteoporosis ( not more than 2 years ).
 It's administered by daily subcutaneous injection. 28-day pre-filled pens available
 Mechanism of Action: Increases osteoblast activity
Optional detailed mechanism : Upregulates expression of pro-osteoblastogenic factors
Modulates the Wnt/beta-catenin signaling pathway Increases Runx2 expression
 Adverse Effects:, orthostatic hypotension Hypercalcemia, hypercalciuria, and theoretical
risk of osteosarcoma after prolonged use

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Calcitonin:
 is a 32-amino-acid polypeptide hormone secreted by the thyroid gland
Uses:
 Hypercalcemia: Synthetic or recombinant calcitonin is used to lower blood calcium
levels, particularly in cases associated with cancer.
 Paget's disease: Calcitonin helps manage pain and neurological complications (e.g.,
hearing loss) associated with severe Paget's disease.
 Osteoporosis: When combined with calcium and vitamin D supplements, calcitonin can
help treat post-menopausal osteoporosis. It is not recommended for long-term therapy
Administration: Calcitonin is administered via injection (subcutaneous) or nasal spray.
Mechanism of action:
 Bone: Inhibits bone resorption by binding to receptors on osteoclasts, slowing down
their activity.
 Kidneys: Reduces the reabsorption of calcium and phosphate in the kidneys.
Adverse effects:
 Injection site pain, Nausea and diarrhea , Flushing among others.
Denosumab (RANKL inhibitor):
 Inhibits osteoclast activity, effective for postmenopausal osteoporosis.
 Administered subcutaneously every 6 months, .
 Well-tolerated but potentially increased risk of infection.
 Optional: RANKL, a crucial cytokine signaling molecule for osteoclastogenesis (bone
resorption).
Cinacalcet (calcimimetic):
 Lowers PTH by activating calcium-sensing receptors.
 Used for secondary hyperparathyroidism and parathyroid carcinoma-induced
hypercalcemia.
 May cause hypocalcemia as a side effect.
Raloxifene (SERM):
 Prevents bone loss in postmenopausal women. Used orally once daily
 Mechanism: Binds selectively to estrogen receptors in bone and other tissues, but acts as
an antagonist in breast tissue.
 Effects:

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 Bone: Stimulates bone formation and inhibits resorption, increasing bone mineral
density (BMD) and reducing fracture risk.
 Endometrium: Protects against thickening and reduces risk of endometrial cancer.
 Adverse effects:
Hot flashes, vaginal dryness, leg cramps, venous thromboembolism (rare).
 Contraindications:
Active pregnancy or breastfeeding.
History of venous thromboembolism.
Unexplained vaginal bleeding.
Known hypersensitivity to Raloxifene.
Glucocorticoids:
 Glucocorticoids are a last-resort option for specific hypercalcemia cases due to their long list of
adverse effects ..
Bisphosphonates
are a class of short-chain organic polyphosphate compounds used to treat osteoporosis , some
other indications Bind to hydroxyapatite crystals in bone, inhibiting osteoclast activity and bone
Optional Inhibiting farnesyl pyrophosphate synthase (enzyme crucial for osteoclast survival).
All drugs end by ronate or ronic ( acid )
Indications:
 Osteoporosis: usually 1st
line for prevention and treatment of most forms, including
postmenopausal osteoporosis, osteopenia, and glucocorticoid-induced osteoporosis.
 Hypercalcemia: Associated with malignancies, especially bone metastases.
 Paget's disease of bone: To suppress osteoclast activity and reduce bone turnover.
Formulations:
 Oral: daily, weekly, or monthly dosing (alendronate, risedronate, ibandronate)
 Injectable: quarterly dosing (ibandronate)
 Intravenous infusion: annual dosing (zoledronate)
Adverse Effects:
 Gastrointestinal:
o Primarily with oral administration
o Esophageal irritation, nausea, vomiting, abdominal pain

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o NB *** Reduced risk by taking with water and avoiding lying down for 30
minutes after taking
 Musculoskeletal:
o Bone pain, muscle aches, joint pain
 Renal impairment:
o More common with high doses and intravenous formulations
 Osteonecrosis of the jaw:
o Rare but serious side effect, especially with long-term use and dental procedures
Contraindications:
 Known hypersensitivity to bisphosphonates
 Hypocalcemia
 Unhealed esophageal lesions
 Abnormal kidney function (for some formulations)
Additional Notes:
 Bioavailability is low (<10%), and food impairs absorption.
 Different bisphosphonates have varying potency and side effect profiles.
Other Drugs details are optional for undergraduate
1. Plicamycin (Mithramycin):
 Antibiotic used for short-term treatment of severe hypercalcemia associated with Paget's
disease or malignancies.
 Reserved due to serious potential side effects:
o Thrombocytopenia
o Hemorrhage
o Hepatic damage
o Renal damage
2. Diuretics:
 Thiazide diuretics (e.g., hydrochlorothiazide):
o May be beneficial in some cases of hypocalcemia.
 Furosemide (Lasix):
o Increases calcium excretion through urine
o Can be useful for treating hypercalcemia, particularly when combined with other
therapies
o

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Management of Severe Hypercalcemia: Summary
 For patients with severe hypercalcemia (calcium > 14 mg/dL or symptomatic):
 Treatment involves a combination of approaches to address volume depletion, bone
resorption, and calcium excretion.
 Immediate therapy:
o Intravenous saline: Corrects volume depletion and enhances calcium excretion.
o Calcitonin: Provides immediate short-term control.
o Bisphosphonates: Preferred for longer-term control (typically zoledronic acid).
 Alternative options for refractory cases or bisphosphonate contraindications:
o Denosumab: May be used in specific situations but requires careful monitoring.
o Dialysis: Considered for severe cases with limitations on hydration.
QUESTIONS
1. Which of the following drugs is routinely added to calcium supplements and milk to prevent rickets in children
and osteomalacia in adults?
(A) Cholecalciferol
(B) Calcitriol
(C) Pamidronate
(D) Teriparatide
2. Which of the following drugs is most useful for the treatment of hypercalcemia in Paget’s disease?
(A) Hydrochlorothiazide
(B) Pamidronate
(C) Raloxifene
(D) Teriparatide
3. The active metabolites of vitamin D act through a nuclear receptor to produce which of the following effects?
(A) Decrease the absorption of calcium from bone
(B) Increase PTH formation
(C) Increase the absorption of calcium from the gastrointestinal tract
(D) Lower the serum phosphate concentration
4. A 59-year-old female was referred to your clinic for evaluation of osteopenia. She was diagnosed with adult-onset
cystic fibrosis (CF). She reported being treated with prednisone 2 times in the past for CF exacerbations. Since
menopause at 52 years of age, she had been treated with raloxifene for osteoporosis prevention. She also was on
daily calcium and vitamin D supplementation. Her bone mineral density test revealed a T score of –1.6 at the
lumbar spine, –2.2 at the left femoral neck, and –1.6 at the total left hip. Which of the following drugs can be used
to reduce the fracture risk by further stimulating bone formation in this patient?
(A) Cholecalciferol
(B) Ergocalciferol
(C) Tamoxifen
(D) Teriparatide
Questions 5–7. A 58-year-old postmenopausal woman was sent for dual-energy x-ray absorptiometry to evaluate
the bone mineral density of her lumbar spine, femoral neck, and total hip. The test results revealed significantly
low bone mineral density in all sites.
5. Chronic use of which of the following medications is most likely to have contributed to this woman’s osteoporosis?

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(A) Lovastatin
(B) Metformin
(C) Prednisone
(D) Propranolol
6. If this patient began oral therapy with alendronate, she would be advised to drink large quantities of water with the
tablets and remain in an upright position for at least 30 min and until eating the first meal of the day. These
instructions would be given to decrease the risk of which of the following?
(A) Cholelithiasis
(B) Constipation
(C) Erosive esophagitis
(D) Pernicious anaemia
7. The patient’s condition was not sufficiently controlled with alendronate, so she began therapy with a nasal spray
containing a protein that inhibits bone resorption. The drug contained in the nasal spray was one of the following.
(A) Calcitonin
(B) Calcitriol
(C) Cinacalcet
(D) Teriparatide
Questions 8–10. A 67-year-old man with chronic kidney disease was found to have an elevated serum PTH
concentration and a low serum concentration of 25-hydroxyvitamin D. He was successfully treated with
ergocalciferol. Unfortunately, his kidney disease progressed so that he required dialysis and his serum PTH
concentration became markedly elevated.
8. Which of the following drugs is most likely to lower this patient’s serum PTH concentration?
(A) Calcitriol
(B) Cholecalciferol
(C) Furosemide
(D) Risedronate
9. Although the drug therapy was effective at lowering serum PTH concentrations, the patient experienced several
episodes of hypercalcemia. He was switched to a vitamin D analogue that suppresses PTH with less risk of
hypercalcemia. Which drug was the patient switched to?
(A) Calcitriol
(B) Cholecalciferol
(C) Furosemide
(D) Paricalcitol
10. In the treatment of patients like this with secondary hyperparathyroidism due to chronic kidney disease, cinacalcet
is an alternative to vitamin D-based drugs. Cinacalcet lowers PTH by which of the following mechanisms?
(A) Activating a steroid receptor that inhibits expression of the PTH gene
(B) Activating the calcium-sensing receptor in parathyroid cells
(C) Activating transporters in the GI tract that are involved in calcium absorption
(D) Inhibiting the farnesyl pyrophosphate synthase found in osteoclasts
11. Bisphosphonates mimic the structure of which endogenous inhibitor of bone resorption?
(a) Vitamin D (b) Estrogen (c) Pyrophosphate ✓ (d) Parathyroid hormone (e) Calcitriol
12. Which of the following side effects is most commonly associated with oral bisphosphonates?
(a) Osteonecrosis of the jaw (b) Hypercalcemia (c) Renal impairment (d) Esophageal irritation ✓ (e) Bone pain
13. Which drug is typically reserved for short-term treatment of severe hypercalcemia due to its potential side effects?
(a) Zoledronic acid (b) Alendronate (c) Risedronate (d) Furosemide (e) Plicamycin ✓
14. Which drug is preferred for longer-term control of severe hypercalcemia?
(a) Calcitonin (b) Denosumab ✓ (c) Thiazide diuretic (d) Plicamycin (e) Zoledronic acid

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15. What is the primary goal of intravenous saline administration in the treatment of severe hypercalcemia?
(a) Inhibit bone resorption (b) Increase calcium excretion (c) Correct volume depletion ✓ (d) Decrease parathyroid
hormone secretion (e) Suppress osteoclast activity
A 58-year-old woman who went through menopause several years ago recently visited her
doctor. She experienced increased aches and pains, particularly in her back and hips,
Investigations revealed significantly low BMD in her lumbar spine, femoral neck, and total
hip.., the doctor prescribed a medication: Comes in tablet form and typically requires once-daily
dosing , Hed advising Sitting upright for at least 30 minutes after taking the medication. what is
the primary concern the doctor is trying to prevent?
(A) postural hypotension
(B) poor absorption
(C) Erosive esophagitis
(D) tachycardia
A 63-year-old man with chronic kidney disease (CKD) previously exhibited elevated
parathyroid hormone (PTH) and low vitamin D levels. Treatment with vitamin D3
(ergocalciferol) successfully controlled his PTH. However, disease progression necessitated
dialysis, leading to a resurgence of significantly elevated PTH. Which of the following
medications is most likely to effectively lower his PTH level?
(A) Calcitriol
(B) Cholecalciferol
(C) Teriparatide
(D) Calcitonin