Patient description: The patient is a 53-year-old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is getting worse. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions of the head and face are detected. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. The serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). The patient's sister had the same problems. She was diagnosed with Paget's disease of bone when she was 52 years old. The diagnosis of Paget's Disease of Bone is confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-60.0,  Risk Factors for or a Diagnosis of Osteoporosis Male or female volunteers 18 to 60 years of age, inclusive Intact normal skin in the area intended for administration Adequate venous access in both upper extremities Dental examination by an appropriately trained professional within 14 days of administration demonstrating no signs, symptoms, or risk factors of osteonecrosis of the jaw (ONJ) Vital signs (BP, HR, temperature, respiratory rate) within normal range or, if out of range, assessed by the Investigator as not clinically significant and it is mutually agreed by both Investigator and Sponsor Medical Monitor that the subject need not be excluded from the study for this reason Electrocardiogram within normal range or if out of range, assessed by the Investigator as not clinically significant and it is mutually agreed by both Investigator and Sponsor Medical Monitor that the subject need not be excluded from the study for this reason Within 14 days prior to administration, metabolic panel (e.g., sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium, AST, ALT, alkaline phosphatase, total bilirubin, albumin, and total protein) and complete blood count within the laboratory normal reference range or, if out of range, assessed by the Investigator as not clinically significant and it is mutually agreed by both Investigator and Sponsor Medical Monitor that the subject need not be excluded from the study for this laboratory value A negative serum or urine pregnancy test (if female of child-bearing potential) within 14 days of study drug administration Female subjects of child-bearing potential must agree to be currently practicing effective birth control or abstinence and agree to continue to do so for at least 30 days after duration of their time on study Decision-making capacity and willingness and ability to comply with the requirements for full completion of the trial  Lower extremity edema Lower extremity pathology that could interfere with any protocol-specified outcome assessment (e.g., cellulitis, lymphatic disorder or prior surgery, pre-existing pain syndrome, auxiliary lymph node dissection, etc.) Creatinine clearance < 60 mL/min (Cockcroft-Gault formula) Any risk factor for bisphosphonate-related renal toxicity including by not limited to known predisposition to or history of renal insufficiency or renal failure, hypertension, diabetes mellitus, volume depletion, sepsis, paraproteinemia, and subjects receiving known nephrotoxic drugs Dehydration Grade 2 or higher based on NCI CTCAE V3.0 Known parathyroid gland dysfunction or any other disease that could lower blood calcium levels Known history and/or electrocardiographic evidence of atrial fibrillation Known allergy to any hyaluronidase Bisphosphonate treatment within preceding six months Known allergy or intolerance to any bisphosphonate