Calcium Loss and Osteoporosis: How Bone Breakdown Works and How to Prevent Fractures Effectively

1. How bone breakdown works: why “calcium loss” becomes osteoporosis

Direct answer: bone is not static stone — it is torn down and rebuilt throughout life (bone remodeling), and adults renew roughly 10% of the skeleton per year.
When resorption exceeds formation for years, bone thins and its internal lattice breaks until it fractures easily
(BHOF Clinician’s Guide 2022).

Osteoclasts vs osteoblasts: the demolition crew and the builders

• Osteoclasts — bone-resorbing cells activated by RANKL; they release acid and enzymes that dissolve bone
• Osteoblasts — bone-forming cells that lay a collagen scaffold for calcium phosphate; they are braked by the protein sclerostin
• Estrogen brakes osteoclasts — after menopause the brake is released, and women may lose about 10–20% of bone mass in the first 5–7 years
• Peak bone mass is reached around age 25–30 and slowly declines afterward; the more you bank when young, the bigger your buffer

Calcium balance: how PTH and vitamin D work

The body stores about 99% of its calcium in bones and teeth; the remaining 1% in blood and cells must stay steady at roughly 8.5–10.5 mg/dL
so the heart, muscles, and nerves can function
(NIH ODS — Calcium).

• When blood calcium starts to fall, the parathyroid glands release PTH → it stimulates bone resorption to release calcium + makes the kidneys reclaim calcium + speeds kidney activation of vitamin D
• Active vitamin D (calcitriol) increases intestinal calcium absorption — with vitamin D deficiency, the gut absorbs only about 10–15% of the calcium you eat
• The result: bone acts as a “calcium bank” — if intake or absorption is short, the body withdraws from bone every day to keep blood levels normal

5. DEXA bone density testing and treatment: reading your T-score and choosing a drug class

Direct answer: DEXA (dual-energy X-ray absorptiometry) measures bone density at the hip and lumbar spine with very low radiation.
Results are reported as a T-score (compared with young adults of the same sex) using WHO criteria, then combined with FRAX to guide treatment
(WHO Study Group 1994).

T-score table: normal vs osteopenia vs osteoporosis

• Z-score (compared with people of the same age) is used instead for premenopausal women and men under 50 — a value ≤ −2.0 means “below the expected range for age” and warrants a search for secondary causes
• A hip or vertebral fracture from minor trauma counts as clinical osteoporosis even if the T-score has not reached −2.5
• FRAX has a Thailand-specific model and uses age, sex, weight, height, risk factors, and femoral neck BMD

When to get tested (international guidance)

• USPSTF 2025: screen all women ≥65, and postmenopausal women under 65 with risk factors after a risk assessment; for men, USPSTF finds the evidence insufficient
  (USPSTF, JAMA 2025)
• Men: the Endocrine Society and BHOF recommend testing at ≥70, or at 50–69 with risk factors
• Before starting medication, doctors usually check for contributing causes: calcium, phosphate, kidney function, ALP, vitamin D, and possibly PTH, thyroid tests, or others as indicated

Osteoporosis drug classes (generic names)

Bisphosphonates

Alendronate and risedronate (weekly tablets), ibandronate (monthly tablet), zoledronic acid (yearly IV infusion) — they bind to bone surfaces and inhibit osteoclasts,
reducing new vertebral fractures by about 40–70% and hip fractures by about 20–40% in pivotal trials
(FIT, Lancet 1996;
HORIZON, NEJM 2007).
Oral forms must be taken on an empty stomach with a full glass of plain water, staying upright for at least 30 minutes (60 for ibandronate); use caution when kidney function (eGFR) is below about 30–35.

Denosumab

A RANKL-blocking antibody injected under the skin every 6 months, reducing new vertebral fractures by about 68% and hip fractures by about 40%
(FREEDOM, NEJM 2009).
Key point: if it is stopped or delayed without follow-on therapy, a rebound occurs — bone density drops quickly and multiple vertebral fractures can follow;
the vertebral fracture rate rose from about 1.2 to 7.1 per 100 patient-years after stopping
(Cummings, J Bone Miner Res 2018).
Doctors therefore always plan a follow-on drug (usually a bisphosphonate); low calcium and vitamin D must be corrected before injection, especially in kidney disease.

Anabolic (bone-building) agents

Teriparatide and abaloparatide (daily injections under the skin, generally for up to about 2 years) intermittently stimulate the PTH receptor so osteoblasts build new bone
(Neer, NEJM 2001: about 65% fewer new vertebral fractures);
romosozumab (monthly injections for 12 months) blocks sclerostin, both increasing formation and reducing resorption — in the ARCH trial it cut new vertebral fractures by about 48% more than alendronate,
but caution is needed after a heart attack or stroke within the past year
(ARCH, NEJM 2017).
After these agents, an antiresorptive must follow to keep the bone gained.

SERMs and menopausal hormone therapy

Raloxifene (a SERM) reduces vertebral fractures but has not been shown to reduce hip fractures, and it raises the risk of venous blood clots.
Menopausal hormone therapy reduced hip fractures by about one-third in the WHI trial
(WHI, JAMA 2002)
and suits selected women — for example, those under 60 or within 10 years of menopause with menopausal symptoms — after weighing breast cancer and clot risk with their doctor.

Data chart: relative reduction in new vertebral fractures in pivotal trials

Each value is versus placebo in its own trial (different populations — not directly comparable) and is not an individual prediction.

Rare risks and dental checks before starting

• Osteonecrosis of the jaw — very rare at osteoporosis doses; risk rises with tooth extraction, decay, gum disease, or poorly fitting dentures
  (ASBMR Task Force 2007)
• Atypical femoral fracture — increases with duration of use and is more common in Asian than white women, yet 3 years of bisphosphonates in 10,000 white women prevented 149 hip fractures versus 2 AFFs
  (Black, NEJM 2020;
  ASBMR 2014)
• Have a dental check and necessary dental work before starting, and always tell your dentist that you take osteoporosis medication
• When risk has fallen after about 3–5 years of bisphosphonates, a doctor may consider a drug holiday — this does not apply to denosumab, and only your doctor should decide

Scientific mechanism (synthesized by the author)

Synthesized by
Asst. Prof. Dr. Norawit Raatpiboon:
bone formation and resorption are governed by the RANKL / RANK / OPG axis — osteoblasts and osteocytes release RANKL, which binds RANK on precursor cells and turns them into osteoclasts,
while osteoprotegerin (OPG) acts as a decoy that traps RANKL. Estrogen raises OPG and suppresses inflammatory cytokines (IL-1, IL-6, TNF-α); when estrogen disappears, RANKL wins, osteoclasts live longer,
and resorption pits deepen until they perforate trabecular struts — gaps that new formation cannot bridge.
On the formation side, osteocytes embedded in bone sense mechanical load; loading reduces sclerostin secretion, releasing the brake on the Wnt pathway so osteoblasts can work — the mechanistic reason resistance exercise helps bone.
Inadequate calcium or low vitamin D causes secondary hyperparathyroidism — continuously (not intermittently) high PTH accelerates resorption, particularly of cortical bone at the hip.
Drugs therefore act at different points: bisphosphonates inhibit farnesyl pyrophosphate synthase in osteoclasts, denosumab binds RANKL in place of OPG,
teriparatide/abaloparatide use intermittent PTH signaling, which paradoxically becomes a building signal, and romosozumab blocks sclerostin directly.
Osteoporosis is thus a disease of the remodeling balance, not of the blood calcium level.