Osteoporotic Baseline — Formation Lagging Resorption
Aging bone loses more than it rebuilds each remodeling cycle.
- ~30: Peak bone mass age (years old)
- 1-3%: Postmenopausal loss (BMD per year)
- ~4-6: Remodeling cycle (months per site)
- 200M+: Global osteoporosis (affected worldwide)
Remodeling imbalance
Resorption briefly outpaces formation in every cycle.
Fracture risk rises
Thinning trabeculae raise fragility fracture odds sharply.
Why anabolic therapy
Antiresorptives only slow loss; anabolics rebuild lost bone.
Teriparatide — Intermittent PTH 1-34 Dosing
Daily brief PTH spikes favor building bone over breaking it down.
- 20 µg/day: Dose regimen (subcutaneous)
- 24: Max approved use (months lifetime cap)
- +9-13%: Spine BMD gain (over 18-24 mo)
- cAMP/PKA: Mechanism (osteoblast pathway)
Pulsatile vs continuous
Short PTH pulses anabolic; continuous exposure turns catabolic.
Osteoblast lifespan
PTH extends osteoblast survival and recruits new precursors.
Duration cap rationale
Rodent osteosarcoma signal set a conservative 24-month limit.
Romosozumab — Unlocking Wnt Signaling
Blocking sclerostin frees Wnt signaling to drive rapid bone gain.
- 210 mg/mo: Dose regimen (two injections)
- 12: Approved course (months only)
- +13%: Spine BMD gain (at 12 months)
- form ↑ / resorb ↓: Dual action (unique profile)
Sclerostin biology
Osteocyte-secreted sclerostin normally brakes Wnt/osteoblast activity.
Antibody mechanism
Romosozumab binds sclerostin, releasing the Wnt brake fast.
Effect wanes by month 12
Formation surge fades, prompting a fixed one-year course.
New Bone Matrix Accrual & Mineralization
Osteoblasts secrete collagen that gradually hardens into new bone.
- ~10: Osteoid mineralization lag (days)
- formation: P1NP marker (surrogate marker)
- resorption: CTX marker (surrogate marker)
- months: Full mineralization (to complete)
Osteoid deposition
New unmineralized collagen matrix is laid down first.
Mineral crystal growth
Hydroxyapatite crystals gradually stiffen the new matrix.
Tracking with P1NP
Rising P1NP reflects active procollagen turnover in real time.
Anabolic-First, Then Antiresorptive Maintenance
Anabolic therapy first, then a bisphosphonate locks in the gains.
- higher: Anabolic-first BMD edge (vs antiresorptive-first)
- DATA/ARCH: Sequencing evidence (trial programs)
- bisphosphonate: Post-romosozumab (recommended)
- years: Gain retention (with maintenance)
Why order matters
Starting antiresorptive first blunts a later anabolic response.
Anabolic then antiresorptive
This order builds bone first, then preserves the gain.
Clinical takeaway
Sequencing choice shapes lifetime fracture-risk reduction.