Osteoporosis-Ca-vitD Flashcards
Treatment of osteoporosis
Majority of OP medications are antiresorptive, aimed to slow bone turnover and increase BMD.
Antiresorptives
Bisphosphonates
Denosumab
Raloxifene
Oestrogen
Anabolic agents
These increase bone formation > resorption to reduce #s. The benefits of anabolic therapy are quickly lost after discontinuation, it is generally recommended to initiate antiresorptive therapy (bisphosphonate or alternative) to maintain bone density gains following a course of teriparatide.
PTH
- Teriparatide is a recombinant form of PTH (it contains 1-34 of its 84 amino acids), commonly used to treat OP in postmenopausal women, or men of high # risk. It acts similar to PTH to stimulate osteoblasts. Osteoblast formation is increased, and osteoblast apoptosis is inhibited, which results in an increase in bone turnover and formation. In addition, it causes a modest increase Ca2+ absorption from GIT and renal tubules. Efficacy has been demonstrated for 18-24months. Should not treat for >2yrs due to risk of bone resorption (must switch to antiresorptive therapy for maintenance). Contra-indicated in pts with Pagets. Montitor for hypercalcemia.
- PTH (containing 1-84 amino acids) is available for pts with chronic hypoparathyroidism despite Vit D / Ca supp’s
PTH receptor protein analogue
- Abaloparatide is a PTHrP analogue that selectively binds to the PTH type 1 receptor, favouring bone formation, has some renal Ca2+ absorption but no GIT abs. Has less adverse effects (hypercalcemia) than teriparatide
Patients with OP who have poor response to treatment with the above
- these patients will have continued bone loss.
- may be due to poor adherence to therapy (the most likely cause; esp w oral bisphosphonates), antiresorptive agent may be of poor choice (too weak), low calcium intake, vit D insufficiency, difference in bioavailability, malabsorption, or that treatment was commenced too late (bone is too severely disrupted), concurrent antiresorptive meds/corticosteroids/PPI (chronic PPI use may lead to increased fractures. Possible explanation - PPI lowers gastric acid levels leading to reduced calcium absorption, secondary hyperPTH, increased bone loss and #s)
- management: ensure adequate intake of calcium supp, check vit D levels, consider alternative treatment (stronger agent, injectable, anabolic agent if already on strong antiresorptive)
https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC2686338/
UpToDate
https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3513863/
https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC2974811/#R47
Bisphosphonates
Zoledronic acid (zolendronate / zometa)
indication:
- Hypercalcemia secondary to cancer
- osteoporosis
Contraindication
CrCl <30ml/min (oncology use); <35 (non-oncology use)
Pre-treatment:
- ensure Ca and vit D adequately replete (unless pt already hypercalcemic then no need to replace either).
- avoid in pregnancy, ensure on adequate birth control
- check renal f^n. (No hepatic adjustment necessary)
SE’s
- flu like syx (give paracetamol post to reduce this)
- lower limb oedema (<21%)
- fatigue (40%)
- GI: nausea/vom (~30-40%), diarrhoea (24%), constip (30%)
- bone pain (50%), anaemia (22-33%), neutropenia, progression of ca
dose: depends on indication
- 4mg IV once for hyperCa2+ of malignancy then re-assess after 1/52 for rpt dose
- every 3-4/52 for metastatic solid tumors / bony lesions in multiple myeloma / androgen-deprivation therapy in prostate cancer
- 3monthly for met breast ca / prostate ca / multiple myeloma
- 5mg IV yearly for fracture prevention
- post-renal transplant bone loss: 4mg IV at week 2, and month 3 post engraftment
Duration
For fracture prevention
- treat for 3years
- if ongoing fracture risk remains high, consider extending duration for up to 6yrs or switch to alternative therapy
- if ongoing fracture risk low after 3yrs (not fragility #s, BMD stable), then give drug holiday for up to 5yrs. Recommence if BMD declining / other risk factors dictate.
Parathyroid physiology
Anatomy
- 4 small glands, posterior thyroid, middle of anterior neck
Function
Ca2+ and Phos homeostasis:
Low serum Ca: (1) Parathyroid gland responds to low serum Ca2+ ; (2) secretes PTH; (3) PTH has many effects (refer below) that ultimately leads to increase in serum Ca2+; (4) serum Ca2+ corrects, leads to less secretion of PTH. Effects of PTH are as follows:
- renal effects: PTH facilitates synthesis of active Vit D (calcitriol) in PCT (by enhacing production of an enzyme required to catalyse this process) + directly increases Ca2+ reabsorption in DCT and collecting duct + decreases Phos reabsorption in PCT (less phos means less Ca-phos precipitates and more ionised Ca)
- bone: PTH directly stimulates osteoblasts to increase RANKL expression (permits differentiation into osteoclasts) + inhibits secretion of osteoprotegrein (permits formation of osteoclasts). Osteoclasts then degrade hydroxyapatite 5)
- Gut: Vit D acts to permit absorption of Ca2+ from small intestine
High serum Ca (negative feedback loop): (1) parathyroid senses high seurm Ca2+; (2) reduces PTH secretion
https://www.ncbi.nlm.nih.gov/books/NBK499940/
