Osteoporosis: a regenerative challenge beyond systemic treatment

Osteoporosis is not limited to an increased risk of fracture; it profoundly alters the intrinsic capacity for bone repair. For the dental surgeon or implantologist, this pathology translates into concrete clinical complications: delayed consolidation, implant loosening, or integration failures of bone substitutes. While conventional systemic therapies (bisphosphonates, denosumab, or anabolic agents) are essential for reducing the overall fracture risk, they do not allow for the reconstruction of localized bone defects or provide immediate mechanical support during a surgical procedure.

This narrative review analyzes biomaterial design strategies specifically tailored to the osteoporotic microenvironment. The objective is to evaluate how scaffolds, targeted delivery systems, and biological platforms can compensate for local deficiencies. The authors explore the hypothesis that a pathology-oriented design approach — simultaneously targeting osteoblast insufficiency, osteoclast hyperactivity, impaired vascularization, and chronic inflammation — could restore tissue integrity where systemic drugs reach their functional limits. The challenge is to transform the passive bone substitute into a bioactive platform capable of regulating a degraded biological niche.

Narrative review methodology

The authors of this work conducted a narrative review of the scientific literature, rather than a formal systematic review, in order to synthesize biomaterial design strategies dedicated to osteoporosis. The objective was to link the specific pathophysiological anomalies of the disease to precise material functions.

The data selection protocol is based on the following parameters:

• Documentary sources: An in-depth search was conducted on the PubMed, Web of Science and Scopus databases.
• Research period: The analysis primarily covers publications between 2000 and 2026, with priority given to studies from the last decade.
• Types of studies included: The review compiles original research articles (in vitro studies and preclinical animal models), literature reviews, clinical guidelines, and translational studies.
• Selection criteria: The studies were selected for their relevance to the pathological barriers of osteoporosis: alteration of osteoblasts, excessive resorption by osteoclasts, reduction of angiogenesis, inflammatory dysregulation, and mechanical fragility.
• Evaluated materials: The analysis segments the devices into scaffolds (ceramics, polymers, composites), targeted delivery systems (nanoparticles, hydrogels), and biological platforms (PRP/PRF, stem cells, extracellular vesicles).

Synthesis of biomaterial design strategies in an osteoporotic context

This narrative review, based on an analysis of the literature published mainly between 2000 and 2026 (PubMed, Web of Science, Scopus), defines the critical parameters for the regeneration of bone defects in patients with osteoporosis. The authors report that the approach must imperatively target the local cellular imbalance, notably the alteration of Wnt/β-catenin signaling and the RANK/RANKL/OPG axis.

Mechanisms of action and therapeutic targets

The synthesis highlights that biomaterials no longer serve solely as passive supports, but as active platforms responding to specific pathophysiological anomalies:

Observations on biological platforms and vectors

The authors highlight the emergence of cell-free solutions and responsive systems:

• Biological systems: Use of PRP/PRF, growth factor-loaded matrices and extracellular vesicles (exosomes) to restore paracrine communication.
• Nanotechnologies: Use of bone-targeting nanoparticles and injectable hydrogels for the controlled release of anabolic molecules (PTH, simvastatin) or nucleic acids.
• Tissue engineering: Development of gene-activated matrices and mesenchymal stem cell (MSC)-loaded scaffolds.

The review concludes that although systemic treatments (bisphosphonates, denosumab, romosozumab) remain the standard for reducing overall fracture risk, biomaterials offer a unique opportunity for direct reconstruction of large bone defects and irregular fracture voids, where pharmacotherapy alone fails to restore local structural integrity.

Analysis of biomaterial strategies in the osteoporotic context

Clinically, this review highlights that the management of a bone defect in an osteoporotic patient cannot be limited to a standard volumetric approach. The failure of conventional grafts is explained by a hostile microenvironment: reduced angiogenesis, low-grade chronic inflammation, and an imbalance in osteoblast/osteoclast coupling. The major interest of this analysis lies in the transition from a passive material toward active platforms capable of restoring angiogenesis and locally modulating bone remodeling.

L'utilisation de biocéramiques dopées au Strontium (Sr) ou au Magnésium (Mg), ainsi que l'intégration de PRP/PRF, offrent des perspectives concrètes pour surmonter l'altération de la matrice extracellulaire. Contrairement aux thérapies systémiques (bisphosphonates, dénosumab) qui réduisent le risque de fracture globale sans reconstruire les défauts localisés, ces stratégies ciblées permettent une stabilisation mécanique immédiate et une libération prolongée d'agents anaboliques.

The weak point of this narrative review remains the translational gap: the majority of evidence relies on animal or in vitro models. For the practitioner, clinical application is still hindered by manufacturing complexity and the lack of standardized protocols for these combined products. The authors are clear: these devices do not replace systemic treatment but must be integrated as an adjuvant local intervention during reconstructive surgeries or fracture fixations.

Study summary

This review (2000-2026) demonstrates that the regeneration of osteoporotic bone requires biomaterials capable of specifically modulating the RANK/RANKL/OPG and Wnt/β-catenin axes. The integration of doped bioceramics (Sr, Mg, Si), biological platforms (PRP/PRF, extracellular vesicles), and gene-activated matrices allows for the local restoration of osteogenesis and angiogenesis, surpassing the limitations of systemic therapies (bisphosphonates, denosumab) when facing critical bone defects.

In concrete terms, for the practitioner:

• Optimize local anchorage: Prioritize bone substitutes doped with Strontium (Sr) or Magnesium (Mg) to inhibit excessive osteoclastic resorption and stimulate osteoblastic differentiation directly at the implant site.
• Support vascularization: In case of low trabecular density, use matrices enriched with PRP/PRF or 3D-printed scaffolds with interconnected porosity to compensate for the angiogenesis deficit in the osteoporotic patient.
• Focus on immunomodulation: Select biomaterials capable of regulating the inflammatory microenvironment to promote a rapid transition to the healing phase and ensure long-term mechanical stability.

Technical lexicon of the study

RANK/RANKL/OPG axis: Molecular signaling system essential for bone homeostasis, whose dysregulation in osteoporosis promotes excessive osteoclastic resorption at the expense of formation.

Sclerostin: Signaling protein contributing to the alteration of bone remodeling; its inhibition is a major therapeutic target to restore the balance between resorption and formation.

Gene-activated matrices: Regenerative platforms integrating genetic material (nucleic acids) to locally induce the production of osteogenic factors by the patient's cells.

Extracellular vesicles (EVs): Biological signaling systems (including exosomes) used to functionalize matrices in order to deliver regenerative paracrine signals without the addition of living cells.

Ionic doping (Strontium/Magnesium): Incorporation of specific ions (Sr, Mg) into bioceramics to stimulate osteoblast differentiation and bone matrix mineralization.

Romosozumab: Therapeutic agent targeting sclerostin, distinguished in the study for its unique ability to simultaneously exert anabolic and anti-resorptive effects.

Osteoconductive scaffolds: 3D structures (ceramics, polymers or composites) serving as a physical support to guide vascular invasion and cellular migration within a bone defect.

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