Background: Targeted therapies like denosumab have revolutionized multiple myeloma (MM) treatment, improved patient outcomes while introducing long-term complications. This study explores a rare instance of delayed maxillary osteonecrosis post-denosumab therapy, delving into its pathophysiology and management. Methods: A 40-year-old male MM patient who developed a painful palatal lesion post denosumab treatment and diagnosed of maxillary osteonecrosis by computed tomography scan and surgical biopsy is presented. Treatment history, symptom progression, and response to the PENTOCLO protocol were analyzed. Results: Post-denosumab discontinuation osteonecrosis highlights its prolonged impact on bone metabolism. PENTOCLO treatment protocol led to significant improvement. Genetic factors influencing osteonecrosis susceptibility have been discussed and considered. Conclusions: This case underscores the need for vigilance regarding long-term complications in MM survivors, preventive strategies, including regular dental evaluations and reducing invasive dental procedures, are crucial. We advocate for an interdisciplinary approach and further research into tailored prevention and management of osteonecrosis in cancer survivors.

BACKGROUND: Peri-implantitis (PI) is a frequent inflammatory disorder characterised by progressive loss of the supporting bone. Not all patients with recognised risk factors develop PI. The aim of this study is to evaluate the presence of single nucleotide polymorphisms (SNP) of inflammatory and bone metabolism related proteins in a population treated with dental implants from the Basque Country (Spain).
METHODS: We included 80 patients with diagnosis of PI and 81 patients without PI, 91 women and 70 men, with a mean age of 60.90 years. SNPs of BMP-4, BRINP3, CD14, FGF-3, FGF-10, GBP-1, IL-1α, IL-1β, IL-10, LTF, OPG and RANKL proteins were selected. We performed a univariate and bivariate analysis using IBM SPSS® v.28 statistical software.
RESULTS: Presence of SNPs GBP1 rs7911 (p = 0.041) and BRINP3 rs1935881 (p = 0.012) was significantly more common in patients with PI. Patients with PI who smoked (> 10 cig/day) showed a higher presence of OPG rs2073617 SNP (p = 0.034). Also, BMP-4 rs17563 (p = 0.018) and FGF-3 rs1893047 (p = 0.014) SNPs were more frequent in patients with PI and Type II diabetes mellitus.
CONCLUSIONS: Our findings suggest that PI could be favoured by an alteration in the osseointegration of dental implants, based on an abnormal immunological response to peri-implant infection in patients from the Basque Country (Spain).

UNASSIGNED: Progressive osseous heteroplasia (POH) is an ultrarare genetic disorder characterized by an inactivating mutation in the GNAS gene that causes heterotopic ossification. Inhibition of the mammalian target of the rapamycin (mTOR) signalling pathway has been proposed as a therapy for progressive bone fibrodysplasia and non-genetic forms of bone heteroplasia. Herein, we describe the impact of using Everolimus as a rescue therapy for an identical twin girl exhibiting an aggressive clinical phenotype of POH.
UNASSIGNED: Clinical evaluation of the progression of the disease during Everolimus treatment was performed periodically. Cytokine markers involved in bone metabolism and protein markers related to bone activity were analyzed to explore bone turnover activity.
UNASSIGNED: The patient received Everolimus therapy for 36 weeks. During treatment, no clinical improvement of the disease was perceived. Analysis of biochemical parameters, namely, β-CTX (r 2 = -0.576, P-value = 0.016) and PNIP (r 2 = -0.598, P-value = 0.011), indicated that bone turnover activity was significantly reduced. Additionally, bone metabolism-related biomarkers showed only a significant positive correlation with PTH levels.
UNASSIGNED: Everolimus treatment did not modify the clinical progression of the disease in an aggressive form of POH, although an impact on the protein markers studied was observed.

Periodontal disease is the second most common oral health problem after dental caries. This increasing prevalence makes it not only a health problem, but also a social issue. The pathogenesis of periodontal disease is associated with a number of adverse exogenous and endogenous factors, including hyperhomocysteinemia (HHcy).
This study aimed to determine the features of bone metabolism in rats with lipopolysaccharide (LPS)-induced periodontitis combined with chronic thiolactone HHcy.
Forty-eight white, non-linear, mature rats were divided into 4 groups: control (n = 12); LPS‑induced periodontitis (n = 12); chronic thiolactone HHcy (n = 12); and periodontitis combined with HHcy (n = 12). The rats were sacrificed the day after the last LPS injection or the day after the last homocysteine (Hcy) thiolactone administration. Bone metabolism was determined based on the activity of alkaline phosphatase (ALP) and acid phosphatase (AP) in blood serum and periodontal homogenate.
A decrease in ALP activity (by 40.1%; р = 0.001) and the mineralization index (MI) (3.5 times; р < 0.001) with an increase in AP activity (2.0 times; р < 0.001) was observed in the periodontal homogenate of rats with LPS‑induced periodontitis. In the case of LPS‑induced periodontitis combined with chronic thiolactone HHcy, more pronounced changes in the activity of phosphatases and in MI were established as compared to rats with LPS‑induced periodontitis only.
Chronic thiolactone HHcy enhances disturbances in bone metabolism in LPS‑induced periodontitis. The osteotoxic effect of HHcy is associated with the activation of osteoclastogenesis and enhanced bone resorption. However, further research is required on the subject.

BACKGROUND: Skeletal manifestations are predominant in psoriatic arthritis (PsA). The aim of this cross-sectional, case-control study is the complex assessment of areal and volumetric bone mineral density (BMD), fracture risk, vitamin D status and bone turnover markers, and its association with disease-related variables.
METHODS: Lumbar spine (L1-L4) and femoral neck (FN) areal, and distal radius (DR) volumetric BMD, 10-year probability of major and hip osteoporotic fracture as assessed by the fracture risk assessment (FRAX) tool, markers of bone metabolism and disease activity were assessed.
RESULTS: Upon comparison of the disease and age- and sex-matched control groups, there was a statistically significant difference in FN areal (0.952 (0.607-1.292) g/cm2 vs. 1.016 (0.760-1.550) g/cm2; p = 0.001) and DR total volumetric (284.3 (138.9-470.3) mg/cm3 vs. 367.0 (287.0-412.0) mg/cm3; p < 0.001) BMD, 10 year probability for major osteoporotic (3.7% (0.7-32%) vs. 2.6% (0-17.5%); p = 0.003) and hip (0.4% (0-16%) vs. 0.05% (0-6.1%); p = 0.002) fracture and 25-hydroxyvitamin D status (47.5 (10-120) nmol/L vs. 64 (10-137; p < 0.001) nmol/L). As compared to areal assessment, volumetric BMD measurements identified a significantly higher number of patients with low bone mineral density (T-Score ≤ - 1.00) (34% vs. 88%, p < 0.001). Upon multiple linear regression analysis, disease activity score, as determined by DAS28 assessment, was an independent predictor of 10-year probability for major osteoporotic fracture (B (95%CI) = 1.351 (0.379-2.323); p = 0.007).
CONCLUSIONS: In the studied PsA cohort, disease activity was an independent predictor of 10-year probability for a major osteoporotic fracture, and complemented assessment of volumetric and areal BMD assured better efficacy at identifying those with low bone mineral density.

Here, we report a case of a patient with symptoms of Cushing syndrome, who is diagnosed with primary generalized glucocorticoid hypersensitivity in the end. The patient\'s relevant laboratory tests and imaging examinations are described. Mifepristone, a glucocorticoid receptor antagonist, was prescribed and its therapeutic effect on the patient\'s electrolyte level, lipid metabolism, and bone metabolism was observed during the treatment. The endocrine assessment indicated normal pituitary-adrenal axis regulation function but reduced cortisol secretion. Quantitative reverse transcription-polymerase chain reaction indicated reduced mRNA level of mineralocorticoid receptor gene. Pituitary magnetic resonance imaging showed normal pituitary anatomy, while adrenal computed tomography scan showed bilateral adrenal atrophy and increased content of visceral and abdominal subcutaneous fat. Moreover, chromosome examination revealed a normal 46, XY chromosome. In this case, mifepristone was administered to treat primary generalized glucocorticoid hypersensitivity. To the best of our knowledge, there are a few reports on mifepristone-treated primary generalized glucocorticoid hypersensitivity. In the one-year follow-up visits, the evaluated results of electrolyte level, lipid metabolism, and bone metabolism indicated that the patient\'s symptoms resulting from cortisol hypersensitivity were relieved progressively.

BACKGROUND: There are a lot study confirmed the relationship of bone serum markers changes and skeletal irregularities. But there is no sufficient case control studies about the role of these markers on bisphosphonate induced osteonecrosis of jaws (BRONJ).
OBJECTIVE: The aim of this study is to find out if there is any derangement of bone markers in bisphosphonate-treated patients with ONJ.
METHODS: We obtained serum bone markers and other relevant endocrine assays on 20 patients with osteonecrosis of the jaw (ONJ) and 20 randomized healthy volunteers. All of the ONJ group treated with zoledronic acid and had been withdrawn from bisphosphonate for at least 6 months. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. The biochemical assays were performed on N-Telopeptides of type I collagen (NTX), bone-specific alkaline phosphatase (ALP), calcitonin, osteocalcin, intact parathyroid hormone (PTH), T3, T4, TSH, and Vitamin D 25 hydroxy (Vit-D).
RESULTS: In ONJ group, PTH level is statistically higher and TSH, Vit-D, osteocalcin and NTX levels statistically lower compared to control group.
CONCLUSIONS: We conclude that these changes in PTH, Vit-D, TSH, osteocalcin and NTX levels maybe have a role in the pathophysiology of BRONJ. But the data need to be confirmed by future studies.

Paget\'s disease of bone (PDB) is a localized, chronic bone metabolic disorder, characterized by an osteoclastic malfunction, causing increased bone resorption and subsequent compensatory creation of new bone with a defective microstructure. Monostotic cases of PDB are less common than asymmetrical polyostotic PDB cases. The radiological diagnosis of PDB is usually straightforward, but monostotic cases can cause diagnostic difficulties. We report a case of monostotic PDB in a 64-year-old man. He experienced pain of the left lower extremity and radiological investigations revealed irregular areas of bone destruction in the left femur. Bone biopsy findings indicated PDB. Treatment with bisphosphonates was initiated, but after about three years of treatment left hip arthroplasty was required due to a large area of bone destruction. Presentation of this case report aims to discuss diagnostic challenges of monostotic cases of PDB and present guidelines of treatment.

Klippel-Trénaunay syndrome (KTS) is described as a complex syndrome characterized by various combinations of capillary, venous, and lymphatic malformations associated with bone and soft tissue hypertrophy. We report a case of a 67-year-old postmenopausal Caucasian women with KTS that shows elevated levels of sclerostin and Dickkopf-related protein 1 (DKK1). Dual-energy X-ray absorptiometry (DXA) BMD T-scores at lumbar spine and femur were normal. Serum calcium and phosphorus levels were consistently normal, 25-hydroxyvitamin D (25OHD) < 30 ng/mL, and normal parathyroid hormone (PTH). Turnover markers (serum osteocalcin [OCN], and carboxy-terminal cross-linking telopeptide of type 1 collagen [CTx]) were in the reference limits. It is interesting to note that the serum levels of sclerostin and DKK-1 were significantly higher in our patient with KTS than in a healthy volunteer (control), without impact on bone mineral density and bone formation markers. In fact, in our patient, the BMD at lumbar spine and femur was normal, and osteocalcin was not suppressed. Based on what is known, we would have expected to find low levels of the inhibitors of the Wnt system, perhaps we can explain the data as a response to the compensation for β-catenin hyper-transformation.

The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density.