Ulrike Schulze-Späte

Palmitic Acid and DGAT1 Deficiency Enhance Osteoclastogenesis, while Oleic Acid‐Induced Triglyceride Formation Prevents It

Both obesity and diabetes mellitus are associated with alterations in lipid metabolism as well as a change in bone homeostasis and osteoclastogenesis. We hypothesized that increased fatty acid levels affect bone health by altering precursor cell differentiation and osteoclast activation. Here we show that palmitic acid (PA, 16:0) enhances receptor activator of NF‐κB ligand (RANKL)‐stimulated osteoclastogenesis and is sufficient to induce osteoclast differentiation even in the absence of RANKL. TNFα expression is crucial for PA‐induced osteoclastogenesis, as shown by increased TNFα mRNA levels in PA‐treated cells and abrogation of PA‐stimulated osteoclastogenesis by TNFα neutralizing antibodies. In contrast, oleic acid (OA, 18:1) does not enhance osteoclast differentiation, leads to increased intracellular triglyceride accumulation, and inhibits PA‐induced osteoclastogenesis. Adenovirus‐mediated expression of diacylglycerol acyl transferase 1 (DGAT1), a gene involved in triglyceride synthesis, also inhibits PA‐induced osteoclastogenesis, suggesting a protective role of DGAT1 for bone health. Accordingly, Dgat1 knockout mice have larger bone marrow‐derived osteoclasts and decreased bone mass indices. In line with these findings, mice on a high‐fat PA‐enriched diet have a greater reduction in bone mass and structure than mice on a high‐fat OA‐enriched diet. Thus, we propose that TNFα mediates saturated fatty acid‐induced osteoclastogenesis that can be prevented by DGAT activation or supplementation with OA.

Dynamics of bone turnover markers in patients with heart failure and following haemodynamic improvement through ventricular assist device implantation.

Abnormal bone metabolism and progressive demineralization have been described in patients with heart failure (HF). We hypothesized that mechanical unloading through implantation of a ventricular assist device (VAD) with subsequent haemodynamic improvement would correct abnormal bone metabolism in patients with advanced HF.

Diet-Induced Obesity and Its Differential Impact on Periodontal Bone Loss

Obesity is associated with abnormal lipid metabolism and impaired bone homeostasis. The aim of our study was to investigate the impact of specific elevated fatty acid (FA) levels on alveolar bone loss in a Porphyromonas gingivalis–induced model of periodontal disease and to analyze underlying cellular mechanisms in bone-resorbing osteoclasts and bone-forming osteoblasts in mice. Four-week-old male C57BL/6 mice were randomly divided in groups and subjected to a palmitic acid (PA)– or oleic acid (OA)–enriched high-fat diet (HFD) (20% of calories from FA) or a normal caloric diet (C group) (10% of calories from FA) for 16 wk. Starting at week 10, mice were infected orally with P. gingivalis (W50) or placebo to induce alveolar bone loss. Animals were sacrificed, and percentage fat, serum inflammation (tumor necrosis factor [TNF]-α), and bone metabolism (osteocalcin [OC], carboxy-terminal collagen crosslinks [CTX], and N-terminal propeptides of type I procollagen [P1NP]) markers were measured. Osteoblasts and osteoclasts were cultured in the presence of elevated PA or OA levels and exposed to P. gingivalis. Animals on FA-enriched diets weighed significantly more compared with animals on a normal caloric diet (P < 0.05). Both obese groups had similar percentages of fat (P = nonsignificant); however, alveolar bone loss was significantly greater in animals that were on the PA-enriched HFD (P < 0.05). TNF-α levels were highest in the PA group (P < 0.001) and increased in all groups in response to P. gingivalis inoculation (P < 0.01), whereas bone remodeling markers OC, CTX, and P1NP were lowest in the PA group (P < 0.001) and highest in the C group. Bacterial challenge decreased bone metabolism markers in all groups (P < 0.01). Further, osteoclasts showed an augmented inflammatory response to P. gingivalis in the presence of hyperlipidemic PA levels as opposed to OA cultures, which responded similarly to controls. These findings indicate that the specific FA profile of diet rather than weight gain and obesity alone modulates bone metabolism and can therefore influence alveolar bone loss.

Relationship of Bone Metabolism Biomarkers and Periodontal Disease: The Osteoporotic Fractures in Men (MrOS) Study.

CONTEXT Periodontitis is an inflammatory disease of tooth-supporting tissue leading to bone destruction and tooth loss. Periodontitis affects almost 50% of adults greater than 30 years of age. OBJECTIVE This study evaluated the association between biomarkers linked to bone formation and resorption with the occurrence and progression of periodontal disease in older men (≥ 65 y). DESIGN The Osteoporotic Fractures in Men (MrOS) study is a prospective, observational study among men 65 years of age and older. SETTING This ancillary study, Oral and Skeletal Bone Loss in Older Men, was conducted at two of the six MrOS study sites (Birmingham, AL and Portland, OR). PATIENTS Patients underwent medical and dental evaluation. Diagnoses of periodontitis were based on clinical attachment loss, pocket depth, calculus, plaque, and bleeding on a random half-mouth. Bone metabolism biomarkers included serum levels of calcium, phosphate (Pi), alkaline phosphatase, albumin, carboxy-terminal collagen crosslinks (CTX), N-terminal propeptides of type I procollagen, isoform 5b of tartrate-resistant acid phosphatase, and urine alpha- carboxy-terminal collagen crosslinks (alpha-CTX) and beta-CTX and serum levels of calciotropic hormones vitamin D (25(OH)D) and PTH. MAIN OUTCOME MEASURES The aim of this study is to correlate bone metabolism biomarkers with prevalence and progression of periodontal disease in older men. RESULTS Patients with more severe periodontitis had significantly higher levels of PTH (P trend = .0004), whereas 25(OH)D was lower (P trend = .001). In a subset of men reevaluated at a second dental visit, improvement of periodontitis was associated with lower alpha-CTX, beta-CTX, and CTX levels at baseline after adjusting for age, site, and body mass index. CONCLUSION This study suggests that a distinct set of biomarkers of bone metabolism are associated with more severe periodontal disease (PTH, 25(OH)D) and periodontal progression (alpha-CTX, beta-CTX, and CTX) over time.

Periodontitis and bone metabolism in patients with advanced heart failure and after heart transplantation

Heart failure (HF) is a multiorgan, pro‐inflammatory syndrome that impairs bone metabolism. Pro‐inflammatory cytokines and bone catabolism enhance periodontal disease, a local inflammatory, bacteria‐induced disease that causes bone loss and periodontal soft tissue destruction.

A prospective clinical trial to assess the optical efficacy of pink neck implants and pink abutments on soft tissue esthetics

OBJECTIVE The purpose of this prospective, randomized, controlled, multicenter clinical study was to analyze the optical effects of an anodized pink colored implant shoulder/abutment system in the peri-implant mucosa of immediately placed dental implants. MATERIALS AND METHOD Forty subjects with a restoratively hopeless tooth in the maxillary esthetic zone, were recruited and randomized to receive either a pink-neck implant, or a conventional gray implant. All patients received an immediate implant and immediate provisional and two identical CAD/CAM titanium abutments with different surface colors: pink and gray, and one zirconia all-ceramic crown. The color of the peri-implant mucosa was measured using a dental spectrophotometer and analyzed using CIELAB color system. RESULTS The overall color difference between the peri-implant mucosa with a pink abutment and a gray abutment was ΔE = 4.22. Patients with gray implants presented a color change of ΔE = 3.86-4.17 with this abutment change, while patients with pink implants had a color change of ΔE = 3.84-4.69. The peri-implant mucosa with a pink abutment was significantly more red when compared with a gray abutment (P ≤ .01). CONCLUSIONS When a pink abutment was used, there is a significant color change of the peri-implant mucosa that is above the detectable color threshold. CLINICAL SIGNIFICANCE Esthetic outcomes are important for the success of implant treatment of maxillary anterior implants. The phenomenon of the gray color of a dental implant and abutment shining through the peri-implant mucosa has been documented in the literature. The objective of this study was to assess the optical effect of an anodized pink-neck implant and a pink abutment on the color of peri-implant mucosa. This study demonstrates that using pink-neck implant and a pink abutment would contribute positively to the overall esthetic outcome for an anterior implant.