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. 2019 Jan 9;98(4):450–458. doi: 10.1177/0022034518818456

Osteoporotic Changes in the Periodontium Impair Alveolar Bone Healing

M Arioka 1,2, X Zhang 1,3, Z Li 1,4, US Tulu 1, Y Liu 1,3, L Wang 3, X Yuan 1, JA Helms 1,✉
PMCID: PMC6429667  PMID: 30626268

Abstract

Osteoporosis is associated with decreased bone density and increased bone fragility, but how this disease affects alveolar bone healing is not clear. The objective of this study was to determine the extent to which osteoporosis affects the jaw skeleton and then to evaluate possible mechanisms whereby an osteoporotic phenotype might affect the rate of alveolar bone healing following tooth extraction. Using an ovariectomized mouse model coupled with micro–computed tomographic imaging, histologic, molecular, and cellular assays, we first demonstrated that the appendicular and jaw skeletons both develop osteoporotic phenotypes. Next, we demonstrated that osteoporotic mice exhibit atrophy of the periodontal ligament (PDL) and that this atrophy was accompanied by a reduction in the pool of osteoprogenitor cells in the PDL. The paucity of PDL-derived osteoprogenitor cells in osteoporotic mice was associated with significantly slower extraction socket healing. Collectively, these analyses demonstrate that the jaw skeleton is susceptible to the untoward effects of osteoporosis that manifest as thinner, more porous alveolar bone, PDL thinning, and slower bone repair. These findings have potential clinical significance for older osteopenic patients undergoing reconstructive procedures.

Keywords: osteoporosis, periodontal ligament, atrophy, tooth extraction, osteogenesis, repair

Introduction

Aging is associated with a global functional decline in tissue homeostasis (Lopez-Otin et al. 2013) and a concomitant slowing of tissue repair (Sgonc and Gruber 2013). In the skeleton, age-related changes typically manifest as osteopenia and osteoporosis, a disease state where bone resorption outpaces bone formation (Kanis et al. 2013). In an osteoporotic state, alkaline phosphatase activity declines, with a commensurate increase in osteoclast activity (Chen, Wang, et al. 2018).

The osteopenic/osteoporotic skeleton is at risk for bone fractures (Rachner et al. 2011), but whether osteoporosis is also associated with slower bone repair remains a matter of some dispute (reviewed by Cheung et al. 2016). For example, the orthopedic literature clearly indicates that in ovariectomy (OVX)–induced osteoporosis animal models, bones heal slower (Namkung-Matthai et al. 2001; He et al. 2011), and even after they are healed, osteoporotic bones are weaker (Meyer et al. 2001). The dental literature, however, is ambiguous. Some data from animal models suggest slower healing (Luize et al. 2008; Chen, Pei, et al. 2018), whereas other data suggest no untoward effects on repair (Ramalho-Ferreira et al. 2017). Clinical data offer few clues. For example, 1 retrospective study on dental implant survival found that patients with osteoporosis had a higher incidence of dental implant loss (Giro et al. 2015), but it was not clear whether osteoporosis itself had detrimental effects on bone healing or if the slower healing was a consequence of other age-related comorbidities (reviewed by de Medeiros et al. 2018).

Here, we attempted to address this knowledge gap by answering 1) whether jaw bones were as susceptible to osteoporotic changes as long bones and 2) if osteoporotic alveolar bone was slower to repair following, for example, tooth extraction. Ideally, we would study the rate of extraction socket healing in elderly rodents. Aging, however, is associated with cellular cementum accrual at the root tips (Huang, Salmon, et al. 2016), which complicates complete tooth removal, and the retention of root tips in an extraction socket can have a significant impact on healing (Pietrokovski 1967). To avoid these issues, OVX was used to induce an osteoporotic phenotype in mice (Kalu and Chen 1999). Since some data suggest that an osteoporotic phenotype takes longer to develop in alveolar bone (Johnston and Ward 2015), we avoided this issue by waiting 8 wk until analysis of the osteoporotic phenotype in the jaw skeleton. Using micro–computed tomographic (µCT) imaging, molecular/cellular assays, and histological assessments, we then evaluated alveolar bone healing following tooth extraction. Our results uncovered a mechanism to explain slower alveolar bone healing in OVX-induced osteoporotic animals. From these data, we draw conclusions that have direct clinical application for procedures ranging from tooth extraction to implant osseointegration in an at-risk older patient population.

Methods and Materials

See Appendix.

Results

OVX Induces a Phenotype in Appendicular and Alveolar Bone That Mimics Age-Related Osteoporosis

Our first objective was to determine if the standard OVX surgery, which reliably produces an osteopenic/osteoporotic phenotype in long bones (Kalu and Chen 1999), also affected alveolar bone. Young skeletally mature mice served as a positive control for optimal bone health (Fig. 1A). OVX mice underwent surgery 8 wk prior and constituted the test group (Fig. 1B). Middle-aged mice served as a control for age-related changes in bone health (Fig. 1C).

Figure 1.

Figure 1.

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Ovariectomy (OVX) produces appendicular and alveolar bone loss that resembles age-related osteoporosis. Representative transverse micro–computed tomographic sections of distal femur in (A) young, (B) OVX, and (C) middle-aged mice. Three-dimensional visualization of trabecular bone in the femur in (D) young, (E) OVX, and (F) middle-aged mice. (G) Quantification of BV/TV, Tb.Th, Tb.N, and Tb.Sp in the 3 age groups. Representative sagittal micro–computed tomographic sections of interradicular bone around mxM1 from (H) young, (I) OVX, and (J) middle-aged mice. Three-dimensional visualization of interradicular bone around mxM1 in (K) young, (L) OVX, and (M) middle-aged mice. (N) Quantification of BV/TV, Tb.Th, Tb.N, and Tb.Sp of alveolar bone. BV/TV, bone volume/total volume; mxM1, maxillary first molar; Tb.N, trabecular number; Tb.Sp, trabecular separation; Tb.Th, trabecular thickness. Scale bars = 500 µm. Values are presented as mean ± standard deviation. *P < 0.05. **P < 0.01. ***P < 0.001.

Volume rendering of the distal femur revealed a dense pattern of trabecular bone in the young cohort (Fig. 1D) whereas trabecular bone mass was significantly reduced (Fig. 1E) in the OVX group, comparable to that observed in the middle-aged group (Fig. 1F, quantified in G). Bone volume/total volume, trabecular number, and trabecular separation were also equivalent in OVX and middle-aged mice (Fig. 1G). These data collectively validated that OVX produces an osteoporotic phenotype in the appendicular skeleton.

In the same groups of mice, alveolar bone was evaluated. Compared with that of the young cohort (Fig. 1H), interradicular bone mass around the maxillary first molar (mxM1) was significantly reduced in the OVX group (Fig. 1I), comparable to that in the middle-aged group (Fig. 1J). Volume rendering and quantification of the interradicular bone around mxM1 (Fig. 1K–M) indicated that bone volume/total volume and trabecular separation in the OVX group were equivalent to that in the middle-aged group (Fig. 1N). Thus, an osteoporotic phenotype was evident in both long bones and alveolar bone.

OVX Results in PDL Atrophy That Is Comparable to Age-Related PDL Atrophy

Since the alveolar bone was notably thinner in osteoporotic mice, we investigated whether these bony changes in the OVX group were also accompanied by alterations in PDL. In the young group, the average mxM1 PDL width was ~86 µm (Fig. 2A, quantified in D). PDL width in the OVX group was significantly reduced at ~71 µm (Fig. 2B, quantified in D), comparable to that in the middle-aged group (Fig. 2C, quantified in D). This represented a decrease in PDL width of 18%, which occurred over the course of 8 wk.

Figure 2.

Figure 2.

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Ovariectomy (OVX) produces periodontal ligament (PDL) atrophy that resembles age-related PDL atrophy. Representative transverse micro–computed tomographic sections through mxM1 from (A) young, (B) OVX, and (C) middle-aged mice. Root surfaces are indicated by yellow lines and alveolar bone surfaces by red lines. The same region (e.g., crestal, middle, or apical) was examined in all 3 groups. (D) Quantification of mxM1 PDL width across the groups. Representative sagittal histologic tissue sections of the intact PDL, evaluated with aniline blue staining in (E) young, (F) OVX, and (G) middle-aged mice and with picrosirius red in (H) young, (I) OVX, and (J) middle-aged mice. ab, alveolar bone; d, dentin; mxM1, maxillary first molar; pdl, periodontal ligament. Scale bars = 500 μm (A–C), 100 μm (E–G, H–J). Values are presented as mean ± standard deviation. *P < 0.05. **P < 0.01. ***P < 0.001.

Histologic analyses verified the µCT findings (Fig. 2E–G): for example, picrosirius red staining indicated that PDL collagen fibers were dense in the young group (Fig. 2H) but slightly sparse in the OVX group (Fig. 2I). For the middle-aged group, PDL collagen fibers were atrophied (Fig. 2J). Since the PDL contains osteoprogenitor cells that directly contribute to alveolar bone turnover (Lin et al. 2000; Saito et al. 2002) and the PDL was notably atrophied in OVX and middle-aged mice, we reasoned that the osteoporotic PDL might also have fewer osteoprogenitor cells. We explored this hypothesis in the next series of experiments.

An Atrophied PDL Contains a Reduced Percentage of Osteoprogenitor Cells

The PDL was visualized by periostin and DAPI immunostaining (Fig. 3A). In the OVX group the number of DAPI+ve cells in PDL were significantly reduced as compared with the young group (Fig. 3B, quantified in D) and was equivalent to the cell density observed in the middle-aged group (Fig. 3C, quantified in D). We identified which cells were osteoprogenitors by immunostaining for the osteogenic transcription factors Osterix and Runx2 (Komori et al. 1997; Nakashima et al. 2002). In the young group, Osterix+ve cells populated the central region of the PDL (Fig. 3E). In the OVX group, the percentage of total cells in the PDL that were Osterix+ve was significantly lower than that in the young group (Fig. 3F, quantified in H) and comparable to that in the middle-aged group (Fig. 3G, quantified in H). Runx2+ve cells were primarily located along the alveolar bone and tooth surfaces (Fig. 3I). In the OVX group, the percentage of total cells in the PDL that were Runx2+ve was significantly lower than that in the young group (Fig. 3J, quantified in L) and comparable to that in the middle-aged group (Fig. 3K, quantified in L). Together these results demonstrated that PDL atrophied as a consequence of OVX surgery and that this atrophy was accompanied by a reduction in osteoprogenitor cells in the PDL.

Figure 3.

Figure 3.

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Osteoporosis is associated with a decline in osteoprogenitor cells, which directly affect the initial stage of bone healing. Representative sagittal sections through the intact periodontal ligament (PDL) show periostin-immunopositive cells in (A) young, (B) ovariectomy (OVX), and (C) middle-aged mice; (D) quantification of DAPI+ve/periostin+ve cells in the PDL. Osterix expression in (E) young, (F) OVX, and (G) middle-aged mice; (H) quantification of Osterix+ve/DAPI+ve cells and Osterix+ve cell number in the PDL. Runx2 expression in (I) young, (J) OVX, and (K) middle-aged mice; (L) quantification of Runx2+ve/DAPI+ve cells and Runx2+ve cell number in the PDL. Representative sagittal sections through the tooth extraction socket on PED1, evaluated for periostin expression in (M) young and (N) OVX mice; (O) quantification of DAPI+ve/periostin+ve cells in tooth extraction sockets. Osterix expression in (P) young and (Q) OVX mice; (R) quantification of Osterix+ve/DAPI+ve cells and Osterix+ve cell number in tooth extraction sockets. Runx2 expression in (S) young and (T) OVX mice; (U) quantification of Runx2+ve/DAPI+ve cells and Runx2+ve cell number in tooth extraction sockets. ab, alveolar bone; d, dentin; es, extraction socket; PED, postextraction day; po, periosteum; ROI, region of interest; TE, tooth extraction. Scale bars = 100 μm. Values are presented as mean ± standard deviation. *P < 0.05. **P < 0.01. ***P < 0.001.

PDL width was significantly (18%) reduced in osteoporotic mice (Fig. 2), and correspondingly, cell density in the PDL was significantly (25%) reduced (Fig. 3A–D). Based on these observations, we asked whether osteoporotic mice had fewer osteoprogenitor cells or, alternatively, if the osteoprogenitor cells from an osteoporotic mouse were less “proficient” at giving rise to new bone.

The absolute number and percentage of PDL cells that were Osterix+ve were significantly (35%) reduced in the PDL of osteoporotic mice (Fig. 3E–H) as compared with young mice. The same was true of Runx2: in an intact state, the absolute number and percentage of PDL cells that were Runx2+ve were significantly (59%) reduced in the PDL of osteoporotic mice (Fig. 3I–L). These data demonstrate that in an atrophied PDL, there are still significantly fewer osteoprogenitor cells in osteoporotic mice.

An Osteoporotic Phenotype Is Associated with a Reduced Osteoprogenitor Cell Population

Osteoprogenitor cells in the PDL maintain alveolar bone volume and contribute to the repair of alveolar bone after injury (Yuan et al. 2018). One strategy to demonstrate that the PDL of OVX mice had a reduced osteoprogenitor cell population was to create a focal injury and then evaluate how it affected the number and percentage of osteoprogenitor cells. We created 2 experimental groups: In the young group, mxM1 extractions were performed, and the rate of extraction socket healing was monitored. In the OVX group, OVX surgery was performed, and mxM1 extractions were performed after an 8-wk period, during which the osteoporotic phenotype developed.

We evaluated the extraction sockets within 24 h of tooth removal. The residual PDL left attached to the socket walls was identified by periostin; in the young group (Fig. 3M), this residual PDL contained significantly more DAPI+ve, periostin+ve cells than in the OVX group (Fig. 3N, quantified in O).

Osteoprogenitor cells in the PDL are triggered to proliferate in response to tooth extraction (Yuan et al. 2018). In osteoporotic mice, the absolute number and percentage of PDL cells that were Osterix+ve osteoprogenitors were significantly (50%) reduced (Fig. 3P, Q, quantified in R). Likewise, the absolute number and percentage of Runx2+ve osteoprogenitors were significantly (73%) reduced (Fig. 3S, T, quantified in U). Thus, the PDL of osteoporotic mice contained fewer osteoprogenitor cells, and this reduced population of progenitor cells persisted even after injury. Our next objective was to determine whether this diminished progenitor pool directly affected the rate of alveolar bone repair.

Analyses of extraction socket healing commenced within 24 h of tooth removal. In young and OVX mice, aniline blue staining revealed blood-filled sockets (Fig. 4A, B). In the young group thick PDL remnants remained (Fig. 4A′); in the OVX group, the PDL remnants were thinner (Fig. 4B′). At this early stage in healing, picrosirius red staining showed no explicit differences in the alignment and density collagen of PDL remnants between the groups (Fig. 4C, D).

Figure 4.

Figure 4.

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An atrophied periodontal ligament (PDL) is associated with a decline in osteoprogenitor cell number. Representative sagittal tissue sections through tooth extraction sockets on PED1, evaluated with aniline blue staining in (A) young and (B) ovariectomy (OVX) mice. Areas indicated with yellow boxes are shown at higher magnification in panels A′ and B′. Adjacent tissue sections from (C) young and (D) OVX mice stained with picrosirius red and viewed under polarized light. Representative sagittal sections of tooth extraction sockets from (E) young and (F) OVX mice, evaluated with DAPI to identify viable cells; (G) quantification of DAPI+ve cells in tooth extraction sockets on PED3. On adjacent tissue sections from (H) young and (I) OVX mice, Ki67 expression identifies proliferating cells; (J) quantification of Ki67+ve/ DAPI+ve cells and Ki67+ve cell number in tooth extraction sockets on PED3. Runx2 expression in (K) young and (L) OVX mice; (M) quantification of Runx2+ve/ DAPI+ve cells and Runx2+ve cell number in tooth extraction sockets on PED3. ab, alveolar bone; es, extraction socket; PED, postextraction day; ROI, region of interest; TE, tooth extraction. Scale bars = 100 μm (A–F, H, I, K, L). Values are presented as mean ± standard deviation. *P < 0.05. **P < 0.01.

By postextraction day (PED) 3, cells residing in PDL remnants migrated into the extraction socket (Yuan et al. 2018; Fig. 4E). In contrast, extraction socket cell density was significantly lower in the OVX group (Fig. 4F, G). Cells residing in these PDL remnants began to proliferate around PED3, which ultimately produced a dense cell infiltrate (Fig. 4H). In the OVX group, the absolute PDL cell number was reduced (Fig. 4I), but the ratio of Ki67+ve cells/total cells in the extraction sockets was not (Fig. 4J). This meant that the OVX phenotype did not impair mitotic activity.

We performed the same analyses with the osteoprogenitor marker Runx2. In extraction sockets of OVX mice, the absolute number of osteoprogenitor cells, as well as the ratio of osteoprogenitor cells:total cells, was significantly reduced (Fig. 4K–M).

An Osteoporotic Phenotype and Slower Extraction Socket Healing Are Associated with a Reduced Wnt-Responsive PDL Population

Did the paucity of osteoprogenitor cells in OVX have any impact on healing rates? Analyses of healing rates at PED7 provided a clear answer: histologic (Fig. 5A, B) and µCT (Fig. 5C, D) data demonstrated that OVX extraction sockets were significantly slower to heal (quantified in Fig. 5E).

Figure 5.

Figure 5.

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An osteoporotic phenotype correlates with fewer Wnt-responsive periodontal ligament (PDL) cells and a slower rate of extraction socket healing. Pentachrome staining to identify new bone in extraction sites of (A) young and (B) ovariectomy (OVX) mice. Representative 3-dimensional visualizations of new bone formed in tooth extraction sockets of (C) young and (D) OVX mice. (E) Quantification of BV/TV in healing extraction sites on PED7. In Axin2CreERT2/+; R26RmTmG/+ mice, Wnt-responsive cells transition from expressing membrane tomato (red) to membrane GFP (green) in the response to tamoxifen delivered on 3 consecutive days. Animals were sacrificed 1 wk later. GFP+ve, Wnt-responsive cells were (F) quantified and expressed as a percentage of total cells in the region of interest; cells were also visualized in the PDLs of (G) young and (H) OVX mice. In a second experiment, tamoxifen was delivered for 3 consecutive days, followed by tooth extraction; mice were euthanized 3 and 7 d after tooth extraction. Wnt-responsive GFP+ve cells in the tooth extraction sockets of OVX mice: (I, J) PED3 and (K, L) PED7. (M) Quantification of GFP+ve cells in tooth extraction sockets at the time points indicated (n = 6). ab, alveolar bone; BV/TV, bone volume/total volume; es, extraction socket; PED, postextraction day. Scale bars = 100 μm (A, B, E–L), 500 µm (C, D). Values are presented as mean ± standard deviation. *P < 0.05. **P < 0.01. ***P < 0.001.

The basis for this slower healing could be traced to a population of Wnt-responsive progenitor cells that reside within the PDL (Yuan et al. 2018). This population of Wnt-responsive cells migrates out of PDL remnants left behind after tooth extraction and directly gives rise to new bone that heals the socket (Yuan et al. 2018). We first asked whether the Wnt-responsive population was affected by an osteoporotic phenotype. Using the Axin2CreERT2/+; R26RmTmG/+ lineage-tracing strain of mice (Yuan et al. 2018), we delivered tamoxifen for 3 d and then examined the distribution of Wnt-responsive cells and their progeny 1 wk later. Compared with the control group, the OVX group had a significantly smaller GFP+ve population (Fig. 5F–H). This was not due to a defect in cell proliferation either: the adult PDL is a quiescent tissue (Huang, Salmon, et al. 2016); consequently, the paucity of GFP+ve cells in the intact PDLs of OVX mice demonstrated that osteoporotic mice had a smaller population of Wnt-responsive cells in their PDLs.

What happened to this Wnt-responsive population following tooth extraction? In control mice, the Wnt-responsive population became mitotically active in response to tooth removal (Yuan et al. 2018). On PED3, the number of Wnt-responsive cells and their progeny dramatically increased, and by PED7, the population had nearly tripled in size (Fig. 5I, K, quantified in M).

In the OVX group, extraction also stimulated proliferation of the Wnt-responsive population (compare Fig. 5H with J, L) to nearly the same degree as in controls (quantified in Fig. 5M). The problem was that despite this proliferative burst, at all time points examined, there remained a deficit of Wnt-responsive cells and their progeny (Fig. 5F). Thus, the slower-to-heal extraction sockets in OVX mice could be traced back to a shortfall in Wnt-responsive osteoprogenitor cells to heal the extraction socket.

Discussion

An OVX-Induced Osteoporotic Mouse Model in Which the Jaw Skeleton Is Impacted by the Disease

OVX creates an aged phenotype in the skeleton, where bone resorption outpaces bone formation, but not all skeletal sites are affected equivalently. For example, T scores are used among patients to define osteoporosis, and these measurements are typically made at the femoral neck and lumbar spine (Sozen et al. 2017). In our model, the T score of the distal femur of OVX mice was 3.8 standard deviations below that of young mice, well within the definition of osteoporosis.

In OVX surgery, the appendicular skeleton is the most profoundly affected, followed by the axial and cranial skeletons (Liu et al. 2015), but the basis for this regional variation is not known. This finding may be at least part of the explanation for the incorrect conclusion that the jaw skeleton is somehow spared in this systemic disease (Esteves et al. 2015; Liu et al. 2015). To the best of our knowledge, there is no T score for osteoporosis in human alveolar bone. While 1 region of the skeleton (e.g., the jawbones) may experience higher forces than another (Mavropoulos et al. 2007), it is unlikely to be the sole explanation for the oft-repeated mistake that the jaw skeleton is invulnerable to the effects of osteoporosis.

There are species-specific differences in the response to OVX. In rats, >12 wk are required to appreciate an osteoporotic phenotype to appear in alveolar bones (Johnston and Ward 2015), whereas in mice, alveolar bone osteoporosis can be observed within 4 wk (Huang, Wu, et al. 2016). To avoid issues related to the onset of osteoporosis in the jaw skeleton, we opted to wait until 8 wk to begin our analyses. These analyses clearly reveal that OVX produces a significant reduction in bone volume/total volume as well as a significant increase in trabecular separation, which are hallmarks of the osteoporosis disease process. Having established a global osteoporotic phenotype, we were now in a position to specifically assess how osteoporosis affected the periodontium and healing after a common dental procedure, tooth extraction.

OVX-Induced Osteoporosis Is Accompanied by PDL Atrophy, Which in Turn Is Associated with Slower Extraction Socket Healing

Aging and osteoporosis are both associated with PDL atrophy (reviewed by Huttner et al. 2009). PDL atrophy is characterized by a poorer quality and quantity of collagen (Lim et al. 2014; Huang, Salmon, et al. 2016) and a diminished ability of the PDL to withstand functional loading (Niver et al. 2011). In turn, a reduction in functional loading leads to further atrophy of the PDL (Niver et al. 2011). In our experiments, atrophy of the PDL was not caused by hypofunction or aging but rather by a disease process (Fig. 2). In young osteoporotic animals, PDL degeneration was accompanied by a deficit of Wnt-responsive osteoprogenitor cells (Figs. 3, 5). This reduced population was associated with significantly slower healing of the extraction socket (Fig. 5).

Whether PDL atrophy caused by loss of function and/or aging has a similar underlying mechanism of action is not known. We speculate that regardless of the causal factors, an atrophied PDL has fewer osteoprogenitor cells and therefore is likely to show a poor repair response. Is PDL atrophy a characteristic finding in osteoporotic patients? There is, to our knowledge, no clinical report that directly addresses this question. Certainly, fibroblast density decreases with age (Krieger et al. 2013), commensurate with an accumulation of cementum (Gupta et al. 2014), and together these 2 events may be sufficient to decrease PDL width in osteoporotic patients. But while it is clear that an atrophied PDL is a hallmark of an aged patient population (Severson et al. 1978), it remains to be determined whether PDL atrophy is a feature of osteoporosis.

Clinical Implications of an Osteoporosis-Associated Decline in Bone Repair

Osteoporosis is a disease of decreased bone mass, bone fragility, and an increased susceptibility to fracture. These bony changes are due to an imbalance in bone remodeling, where bone resorption outpaces bone formation. In reconstructive surgery, new bone formation is a prerequisite for healing and for implant osseointegration. Animal models draw a definitive positive correlation between osteoporosis and a delay in bone healing (Walsh et al. 1997; Namkung-Matthai et al. 2001; Luize et al. 2008; He et al. 2011; Chen, Wang, et al. 2018). Likewise, some clinical studies demonstrate that osteoporotic patients exhibit a delay in bone healing (Cattermole et al. 1997; Chao et al. 2004), an increase in marginal bone loss (de Medeiros et al. 2018), and an increased failure rate for implants (Moy et al. 2005; Giro et al. 2015). There are, however, few studies that show a definitive correlation between patients with uncontrolled osteoporosis and delayed unions, nonunions, and other defects in bone healing.

If PDL atrophy is synonymous with diminished healing potential in the jaw skeleton, then this factor should be carefully considered in reconstructive plans for elderly patients. For example, it may be appropriate to extend the interval between surgical interventions and reconstructive procedures. For older patients—and those with uncontrolled osteopenia/osteoporosis—it may be advisable to allocate a longer period to allow for complete bone healing, even of simple extraction sockets. Likewise, extending the healing interval may be advisable for older patients to allow time for sufficient new bone to form around implants that are placed in healed extraction sockets. Despite these precautions, it should be emphasized that our data clearly demonstrate that new bone forms in osteoporotic animals (Fig. 5); therefore, aging and/or osteoporosis is not a contraindication for dental implant therapy. Medical conditions such as osteoporotic status, however, should be considered during treatment planning and factored into the informed consent process (Otomo-Corgel 2012).

One therapeutic approach that shows promise in preclinical studies is to reactivate, via a Wnt protein–based therapy, stem and osteoprogenitor cells residing in the periodontium (Yuan et al. 2018). Wnts are potent bone-forming agents, and Wnt signaling regulates bone homeostasis and repair and declines with age (Roforth et al. 2014); consequently, a therapeutic strategy that transiently increases the Wnt signaling of elderly and osteoporotic patients at sites requiring bone reconstruction may be of considerable value.

Author Contributions

M. Arioka, contributed to conception, design, data acquisition, analysis, and interpretation, drafted the manuscript; X. Zhang, Z. Li, U.S. Tulu, Y. Liu, L. Wang, contributed to data acquisition, analysis, and interpretation, critically revised the manuscript; X. Yuan, contributed to data analysis and interpretation, critically revised the manuscript; J.A. Helms, contributed to conception, design, data analysis, and interpretation, drafted and critically revised the manuscript. All authors gave final approval and agree to be accountable for all aspects of the work.

Supplemental Material

DS_10.1177_0022034518818456 – Supplemental material for Osteoporotic Changes in the Periodontium Impair Alveolar Bone Healing
Click here for additional data file. (385.6KB, pdf)

Supplemental material, DS_10.1177_0022034518818456 for Osteoporotic Changes in the Periodontium Impair Alveolar Bone Healing by M. Arioka, X. Zhang, Z. Li, U.S. Tulu, Y. Liu, L. Wang, X. Yuan and J.A. Helms in Journal of Dental Research

Acknowledgments

We thank Kavita Ramnath for assistance in evaluating cementum accumulation in the root tips of middle-aged animals.

Footnotes

A supplemental appendix to this article is available online.

This work is supported by a grant from the National Institutes of Health (R01 DE024000-12 to J.A.H.) and a grant from Kyushu University to M.A.

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

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Supplementary Materials

DS_10.1177_0022034518818456 – Supplemental material for Osteoporotic Changes in the Periodontium Impair Alveolar Bone Healing
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Supplemental material, DS_10.1177_0022034518818456 for Osteoporotic Changes in the Periodontium Impair Alveolar Bone Healing by M. Arioka, X. Zhang, Z. Li, U.S. Tulu, Y. Liu, L. Wang, X. Yuan and J.A. Helms in Journal of Dental Research

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