OSTEOPOROSIS AND WHAT TO DO AFTER A VERTEBRAL FRACTURE Lydia Au Geriatrics Ng Teng Fong Hospital
LET S START WITH WHAT YOU WANT TO KNOW AND DO WITH A VERT FRACTURE
Vertebral fractures Most common (550K per year) Vert fracture is a marker for future fracture risk Klotzbuecher CM, et al. J Bone Miner Res. 200;15:721 Only 25-30% of VF seen on x ray are diagnosed clinically
Vertebral fractures Back pain, disability or physical deformity Increase in mortality related to frailty, comorbities Reduced pulmonary function 1 Compression of internal organs 1 Harrison, et al. J Bone Miner Res. 2007; 22:447-457
Differential diagnosis of spinal fractures Metastasis Multiple Myeloma
Suggested routine investigations: Relevant radiographs to document fractures. Full blood count, ESR. Creatinine, calcium, phosphate total protein,albumin, AST, ALP. 25(0H)vitD TSH Urinalysis to look for haematuria, proteinuria
Vertebral X-Ray Point Placement Hp (posterior) Hm (middle) Ha (anterior)
Calcium Intake Dietary recommendation >65 =1000mg/day Calcium with vitamin D supplements decrease fracture risk in deficient women No benefits > 2000mg daily Misconception that having an adequate daily calcium intake protects against osteoporosis
Vitamin D <65 years of age - 400IUdaily > 65 years of age, esp housebound or nutritionally deprivedsupplementary -800-1000 IU daily cutaneous vitamin D from sun exposure and a balanced diet assures adequate vitamin D Muscle strength Balance Lower extremity function Risk of falling Adequacy Vitamin D BMD Fractures a Vitamin D inadequacy <30 ng/ml; b Vitamin D adequacy 30 ng/ml PTH = parathyroid hormone; BMD = bone mineral density Adapted from Parfitt AM, et al. Am J Clin Nutr. 1982;36:1014 1031; Allain TJ, Dhesi J. Gerontology. 2003;49:273 278; Holick MF. Osteoporos Int. 1998;8(suppl 2):S24 S29; DeLuca HF. Metabolism. 1990;39(suppl 1):3 9; Lips P. Suboptimal vitamin D status: a risk factor for osteoporosis? In: Draper HH, ed. Advances in Nutritional Research. Vol 9. New York: Plenum Press; 1994:151 165; Pfeiffer M, Minne HW. Trends Endocrinol Metab. 1999;10:417 420; Lips P, et al. J Intern Med. 2006;260:245 254; Bischoff-Ferrari HA, et al. Am J Clin Nutr. 2006;84:18 28.
Fall Prevention No good evidence that fracture risk can be modified by preventing falls Home environment made safer Risk further be reduced by The treatment of cataracts Prudent use of medicines especially sedative drugs Specific exercises to improve balance and muscle strength Proper foot wear Comprehensive geriatric assessment to detect illness in the elderly before they manifest with unsteady gait and falls
DEFINITION OF OSTEOPOROSIS characterized by low bone mass with micro architectural disruption and skeletal fragility, resulting in an increased risk of fracture
Diagnostic categories for osteoporosis and low bone mass based upon BMD measurement by DXA Category Bone mass NORMAL LOW BONE MASS (OSTEOPENIA) OSTEOPOROSIS SEVERE (ESTABLISHED) OSTEOPOROSIS A value for BMD within 1 SD of the young adult female reference mean (T-score greater than or equal to -1 SD). A value for BMD more than 1 but less than 2.5 SD below the young adult female reference mean (Tscore less than -1 and greater than -2.5 SD). A value for BMD 2.5 or more SD below the young adult female reference mean (T-score less than or equal to -2.5 SD). A value for BMD more than 2.5 SD below the young adult female reference mean in the presence of one or more fragility fractures.
Clinical Evaluation Differential diagnosis for low BMD Hyperparathyroidism Multiple myeloma Osteomalacia Renal osteodystrophy Chronic liver disease
Pre-treatment evaluation Uncorrected hypocalcemia and suboptimal Vit D levels Vit D how high is enough? Kidney functions, creatinine clearance must be 30-35 ml/min Dental screening 5,6 5. Rosen HN. Risks of bisphosphonate therapy in patients with osteoporosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on 18 Mar, 2017) 6. Hughes BD. Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on 18 Mar, 2017)
PharmacologicTreatment in postmenopausal women and men 50 yrs History of hip or vertebral fracture. T-score -2.5 (DXA) at the femoral neck or spine, after appropriate evaluation to exclude secondary causes. T-score between -1 and -2.5 at the femoral neck or spine, and a 10- year probability of hip fracture 3 % or a 10-year probability of any major osteoporosis-related fracture 20 %
Bisphosphonates gold standard Increase bone mass and hence bone strength Good data on preventing both spine and hip fractures Once monthly administration available Longest safety and efficacy data: 10 years (alendronate, FOSAMAX ) Fosamax: 70 mg once a week Risidronate 150 mg once a month
Contraindications Esophageal disorders, especially with reduced esophageal clearance [Oral] Stricture, achalasia, varices, Barrett s esophagus, etc Active Upper GI problems Dysphagia* Inability to follow administration instructions [Oral] Stay upright for 30 mins Certain Bariatric Surgery w surgical anastomoses in GIT (e.g. Roux-en-Y gastric bypass) [Oral] 1,2 Planned dental implant or extraction- to delay initiation [All] 3,4,5 1. Rosen HN. The use of bisphosphonates in postmenopausal women with osteoporosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on 18 Mar, 2017) 2. Australian Medicines Handbook 2017 (online). Adelaide: Australian Medicines Handbook Pty Ltd; 2017 January. Available from: http://amhonline.amh.net.au/ 3. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw:a systematic review and international consensus. J Bone Miner Res2015;30:3 4. Mavrokokki T, Cheng A, Stein B, Goss A. Nature and fre- quency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 2007;65: 415 23. 5. Rosen HN. Risks of bisphosphonate therapy in patients with osteoporosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on 18 Mar, 2017)
Monitoring for Adverse Drug Reactions Upper GI side effects (reflux, esophagitis, esophageal ulcers) Musculoskeletal symptoms AF Flu-like symptoms for IV Zoledronic Acid Rarely severe bone, joint, and/or muscle pain Risk associated with IV zoledronate shown in HORIZON Pivotal Fracture Trial. Not all trials showed link Evidence on oral bisphosphonates is conflicting. Atypical femur fracture Median treatment duration: 7 years Up to 5 years not associated with the risk Unilateral atypical fracture increases the risk of fracture in the contralateral femur. Withdrawal of bisphosphonates reduces the risk. Proper oral hygiene and regular dental check up 5 5. Rosen HN. Risks of bisphosphonate therapy in patients with osteoporosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on 18 Mar, 2017)
Duration of treatment DISCONTINUING THE DRUG Oral bisphos for five years / ZA once yearly for three years stable BMD, no previous vertebral fractures low risk for fracture in the near future (grade 2C). UP TO 10 YEARS (ZA- UP TO 6 YEARS.) history of osteoporotic fracture before or during therapy t-score below -3.5 in the absence of fractures RESTART BISPHOSPHONATES persistent bone loss (approximately 5 %) at the femoral neck on at least two dual-energy x-ray absorptiometry (dxa) measurements taken at least two years apart, using the same make and model dxa scanner.
Denosumab- inhibition of RANKL fully human monoclonal antibody - high affinity and specificity for RANK L. reduces the differentiation, activity and survival of osteoclasts, thereby slowing the rate of bone resorption. increase BMD and reduce bone turnover in postmenopausal women with low BMD. Decreased risk of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis Subcut 60 mg once in 6 months $352 + injection fee per 6 months Increased fracture risk if stopped > 7 months No need drug holiday
Teriparatide ((parathyroid hormone 1-34) Binds to the same receptors as natural PTH Bone forming effect, reduced bone turnover Reduce vertebral and non-vertebral fractures in women with prior vertebral fractures. Steroid induced: head on trial with alendronate- 90 % reduction in fracture risk $900- $1000 / month Daily subcutaneous injection for 24 months Nausea and vomiting most common. Transient < 2 weeks Contraindications Hypercalcemia Renal clearance less then 30 mmol/l Bone cancers. Paget's
What is considered as successful treatment? BMD stable or increasing and no fractures present Bone turnover markers at or below median value for premenopausal women for patients on antiresorptive agents One fracture is not necessarily evidence of failure. Consider alternative therapy or reassessment for secondary causes of bone loss for patients who have recurrent fractures while on therapy
Common medications that affect bone loss Glucocorticoids Proton pump inhibitors Selective serotonin reuptake inhibitors Anti convulsants Hormonal/ endocrine therapies (aromatase inhibitors, GnRH Calnferotti L, Brandi ML. pathogenesis of osteoporosis. Osteoporsis : future Medicine Led; 2013:6-21
Persons Who Should Be Referred to Specialist Centre: Young patients (premenopausal) Male patients Patients on long-term steroids Patients with disproportionately low Z scores Patients with endocrine disease Patients with metabolic bone disease Patients with other causes of pathological fracture