Variety of different bone substitutive materials are synthetized to improve bone healing potentials in pathological bone conditions. Physiologically active molecules within biomaterials, can initiate expression level of biomarkers, regulating bone remodeling. Aim of our study was to analyze bone healing process in bone defects followed by implantation with 5 % strontium substituted hydroxyapatite (HAP)/tricalcium phosphate (TCP) 70/30 granules (group A) or HAP/TCP biphasic ceramic granules without strontium substitution (group B), or sham surgery affected bone (group C) in osteoporotic rabbits’ femur. Tissue samples from contralateral intact left leg were used for evaluation of systemic effects after surgery. Changes of bone volume were measured and appearance of OPG, NFkB-105, OC, COL-1, BMP-2/4, MMP-2, TIMP-2, IL-1 and IL-10-positive osteocytes in osteoporotic rabbits’ bone defect were evaluated. No statistical difference between groups of trabecular bone volume was detected. All analyzed markers showed higher appearance of positive osteocytes in groups A and B with comparison to control left leg (p < 0.05). Only NFkB105-positive cells showed important difference between sham surgery affected leg and control one (p = 0.034). Numerous OPG-positive cells appeared in group A, while moderate number of them was found in groups B and C (p = 0.025; p = 0.027). Numerous to abundant OC-positive osteocytes were detected in group A, while moderate in group C (p = 0.034). Statistical difference of rest biomarkers between groups was not detected. We concluded that implantation of biomaterials in osteoporotic bone improves local bone regenerative properties. However, the notable increase of OPG-containing cells proves the increase of osteoclastogenesis suppression and gives the evidence for renew of bone functionality.