Correlation between Bone Mineral Density and Progression of Hip Osteoarthritis in Adult Men and Women in Bulgaria—Results from a 7-Year Study

Abstract

Changes in clinical presentation, radiographic progression (RP), bone mineral density (BMD), bone turnover (BT), and cartilage turnover (CT) markers were compared in two groups of patients with hip osteoarthritis (HOA) over a period of 7 years. Each group consisted of 150 patients, including a control group on standard-of-care therapy (SC) with simple analgesics and physical exercises, and a study group (SG) on standard-of-care therapy supplemented by vitamin D3 and intravenous administration of zoledronic acid (5 mg) yearly for 3 consecutive years. Patient groups were homogenized regarding the following: (1) radiographic grade (RG), including 75 patients with hip OA RG II according to the Kellgren–Lawrence grading system (K/L), and 75 with RG III on K/L; (2) radiographic model (RM), as each of the K/L grades was subdivided into three subgroups consisting of 25 patients of different RMs: atrophic (‘A’), intermediate (‘I’), and hypertrophic (‘H’); (3) gender-equal ratio of men and women in each subgroup (Female/Male = 15/10). The following parameters were assessed: (1) clinical parameters (CP), pain at walking (WP-VAS 100 mm), functional ability (WOMAC-C), and time to total hip replacement (tTHR); (2) radiographic indicators(RI)—joint space width (JSW) and speed of joint space narrowing (JSN), changes in BMD (DXA), including proximal femur (PF-BMD), lumbar spine (LS-BMD), and total body (TB-BMD); (3) laboratory parameters (LP)—vitamin D3 levels and levels of BT/CT markers. RV were assessed every 12 months, whereas CV/LV were assessed every 6 months. Results: Cross-sectional analysis (CsA) at baseline showed statistically significant differences (SSD) at p < 0.05 in CP (WP, WOMAC-C); BMD of all sites and levels of CT/BT markers between the ‘A’ and ‘H’ RM groups in all patients. Longitudinal analysis (LtA) showed SSD (p < 0.05) between CG and SG in all CP (WP, WOMAC-C, tTHR) parameters of RP (mJSW, JSN), BMD of all sites, and levels of CT/BT markers for all ‘A’ models and in 30% of ‘I’-RMs (those with elevated markers for BT/CT at baseline and during the observation period). Conclusion: The presence of SSD at baseline (‘A’ vs. ‘H’) supported the thesis that at least two different subgroups of HOA exist: one associated with ‘A’ and the other with ‘H’ models. D3 supplementation and the intravenous administration of bisphosphonate were the treatment strategies that slowed down RP and postponed tTHR by over 12 months in the ‘A’ and ‘I’ RM with elevated BT/CT markers.

Endophenotypes of Primary Osteoarthritis of the Hip Joint in the Bulgarian Population over 60 Years Old

“…We performed additional statistical processing of patient data from two published, double-blinded, randomized, and placebo-controlled studies (DB-RCTs), which tested the effect of ia-CS, ia-HA (KИ-109-3-0008/14.01.2014) [31], and iv-BP (ZA) [34] -KИ-109-3-0009/14.01.2014 www.bda.bg. The results were compared with the country's standard pHOA-D3 supplementation according to serum levels (20-120 ng/mL; target level of 60 ng/mL), simple analgesics (paracetamol, up to 2.0 g/24 h), and physical exercises.…”

“…Among the respective RPs are established differences in radiograph progression [15][16][17][18][19][20][21], as well as differences in biomarkers of bone, cartilage, and synovial turnover [22][23][24][25], and in total and local bone mineral density (BMD) [26][27][28]. There are different therapeutic responses to different pharmacologic medications: ia-CS [29][30][31], ia-HA [31], NSAIDs, antibodies to neuronal growth factor [24,25], and oral and intravenous bisphosphonates [32][33][34]. At present, there are four established basic endophenotypes of primary HOA based upon RPs, BMD, and markers of bone, cartilage, and synovial turnover [22][23][24][25]35]: hypertrophic ('H'-HOA), intermediate ('I'-HOA), atrophic ('A'-HOA), and rapidly progressive ('RP'-HOA).…”

Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights

“…Furthermore, E2 treatment protected against ovariectomy-induced loss of subchondral trabecular bone [123]. While zoledronate acid improved clinical symptoms and delayed THA in patients with HOA with increased bone turnover [124], some studies have reported its non-protective effect against KOA [125]; hence, its protective effects remain inconclusive. Sr ranelate has been widely reported for its efficacy against OA [126,127].…”

Impact of the Indicator ‘Radiographic Pattern’ on the Clinical Presentation and Radiographic Progression of Hip Osteoarthritis - Results from an 8-Year Study

“…Later, the occurrence rate of the different patterns and their association with the clinical and radiological progression of HOA were determined [40][41][42] and a suggestion of presence of different phenotypes in HOA was made [43,44]. The studies on the association between osteoporosis and the pathogenesis and progression of HOA, based on the Rotterdam cohort study [45][46][47], and others [48] proved that 'A'-patterns are associated with a low regional (FN-BMD/TH-BMD) and whole body (LS-BMD and TB-BMD) bone mineral density and a rapid radiographic progression, while 'H'patterns are associated with an increased local BMD and a slow radiographic progression [45][46][47][48]. Currently, HOA radiographic patterns are defined based on the balance between the processes of narrowing of the joint space (as a result of AC -loss) and the processes of SB remodeling with the growth of osteophytes, subchondral sclerosis and the formation of bone cysts, all of them being included in the OARSI atlas for defining HOA [49].…”

“…But it is important to remember that the 'RPs' of the HOA reflects the changes mainly in the SB, i.e. their meaning is different depending on the type of therapeutic intervention.With interventions directly influencing the SB (therapies with bisphosphonates, strontium ranelate, teriparatide, calcitonin, oateoprotegerin) -the changes in SB occur faster and are significant, the importance of RPs is more pronounced and is demonstrated earlier [48,76,77]. On the contrary -with interventions influencing mainly AC (IA-HA, IA-PRP -platelet rich plasma, mesenchymal stem cells -MSCs) [24,[29][30][31][32][33][34][35][36][37][78][79][80][81][82][83] or ST /SS -the smoldering synovitis (IA-CS, methotrexate, anti inflammatory cytokines) [23][24][25][26][27][84][85][86] -the changes in SB are delayed in time and not so obvious, and the influence of RPs on the obtained results occurs later in time and is not so dramatic.…”