Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
International Urogynecology Journal
Published in: International Urogynecology Journal 12/2016

01-12-2016 | Review Article

Prevention of pelvic floor disorders: international urogynecological association research and development committee opinion

Authors: Tony Bazi, Satoru Takahashi, Sharif Ismail, Kari Bø, Alejandra M. Ruiz-Zapata, Jonathan Duckett, Dorothy Kammerer-Doak

Published in: International Urogynecology Journal | Issue 12/2016

Login to get access

Abstract

Introduction and hypothesis

Pelvic floor disorders (PFD), including urinary incontinence, anal incontinence, and pelvic organ prolapse, are common and have a negative effect on the quality of life of women. Treatment is associated with morbidity and may not be totally satisfactory. Prevention of PFDs, when possible, should be a primary goal. The purpose of this paper is to summarise the current literature and give an evidence-based review of the prevention of PFDs

Methods

A working subcommittee from the International Urogynecological Association (IUGA) Research and Development (R&D) Committee was formed. An initial document addressing the prevention of PFDs was drafted, based on a review of the English-language literature. After evaluation by the entire IUGA R&D Committee, revisions were made. The final document represents the IUGA R&D Committee Opinion on the prevention of PFDs.

Results

This R&D Committee Opinion reviews the literature on the prevention of PFDs and summarises the findings with evidence-based recommendations.

Conclusions

Pelvic floor disorders have a long latency, and may go through periods of remission, thus making causality difficult to confirm. Nevertheless, prevention strategies targeting modifiable risk factors should be incorporated into clinical practice before the absence of symptomatology.
Literature
1.
Dieter AA, Wilkins MF, Wu JM (2015) Epidemiological trends and future care needs for pelvic floor disorders. Curr Opin Obstet Gynecol 275:380–384CrossRef
2.
Minassian VA, Drutz HP, Al-Badr A (2003) Urinary incontinence as a worldwide problem. Int J Gynaecol Obstet 82:327–338CrossRefPubMed
3.
Wu JM, Matthews CA, Conover MM, Pate V, Jonsson Funk M (2014) Lifetime risk of stress urinary incontinence or pelvic organ prolapse surgery. Obstet Gynecol 123:1201–1206CrossRefPubMedPubMedCentral
4.
American Urological Association; Society of Urodynamics, Female Pelvic Medicine, Gormley EA, Lightner DJ, Faraday M, Vasavada SP (2015) Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol 193:1572–1580CrossRef
5.
Handa VL, Blomquist JL, Knoepp LR, Hoskey KA, McDermott KC, Muñoz A (2011) Pelvic floor disorders 5–10 years after vaginal or cesarean childbirth. Obstet Gynecol 118:777–784CrossRefPubMedPubMedCentral
6.
MacLennan AH, Taylor AW, Wilson DH, Wilson D (2000) The prevalence of pelvic floor disorders and their relationship to gender, age, parity and mode of delivery. BJOG 107:1460–1470CrossRefPubMed
7.
Gyhagen M, Bullarbo M, Nielsen T, Milsom I (2013) The prevalence of urinary incontinence 20 years after childbirth: a national cohort study in singleton primiparae after vaginal or caesarean delivery. BJOG 120:144–151CrossRefPubMed
8.
Gyhagen M, Bullarbo M, Nielsen TF, Milsom I (2013) Prevalence and risk factors for pelvic organ prolapse 20 years after childbirth: a national cohort study in singleton primiparae after vaginal or caesarean delivery. BJOG 120:152–160CrossRefPubMed
9.
Wilson D, Dornan J, Milsom I, Freeman R (2014) UR-CHOICE: can we provide mothers-to-be with information about the risk of future pelvic floor dysfunction? Int Urogynecol J 25:1449–1452CrossRefPubMed
10.
Norwegian EPINCONT Study, Rortveit G, Daltveit AK, Hannestad YS, Hunskaar S (2003) Urinary incontinence after vaginal delivery or cesarean section. N Engl J Med 348:900–907CrossRef
11.
Vergeldt Tineke FM, Weemhoff M, IntHout J, Kluivers KB (2015) Risk factors for pelvic organ prolapse and its recurrence: a systematic review. Int Urogynecol J J26:1559–1573CrossRef
12.
Mous M, Muller SA, de Leeuw JW (2008) Long-term effects of anal sphincter rupture during vaginal delivery: faecal incontinence and sexual complaints. BJOG 115:234–8CrossRefPubMed
13.
Schwertner-Tiepelmann N, Thakar R, Sultan AH, Tunn R (2012) Obstetric levator ani muscle injuries: current status. Ultrasound Obstet Gynecol 39:372–383CrossRefPubMed
14.
Dietz HP, Simpson JM (2007) Does delayed child-bearing increase the risk of levator injury in labour? Aust N Z J Obstet Gynaecol 47:491–495CrossRefPubMed
15.
Hijaz A, Sadeghi Z, Byrne L, Hou JC, Daneshgari F (2012) Advanced maternal age as a risk factor for stress urinary incontinence : a review of the literature. Int Urogynecol J 23:395–401CrossRefPubMed
16.
Leijonhufvud A, Lundholm C, Cnattingius S, Granath F, Andolf E, Altman D (2012) Risk of surgically managed pelvic floor dysfunction in relation to age at first delivery. Am J Obstet Gynecol 207:303.e1–303.e7CrossRef
17.
Jander C, Lyrenas S (2001) Third and fourth degree perineal tears. Predictor factors in a referral hospital. Acta Obstet Gynecol Scand 80:229–234PubMed
18.
Beckmann, Michael M, Stock, Owen M (2013) Antenatal perineal massage for reducing perineal trauma. Cochrane Database Syst Rev 4
19.
Brito LG, Ferreira CH, Duarte G, Nogueira AA, Marcolin AC (2015) Antepartum use of Epi-No birth trainer for preventing perineal trauma: systematic review. Int Urogynecol J 26:1429–1436CrossRefPubMed
20.
Boyle R, Hay-Smith JE, Cody JD, Morkved S (2012) Pelvic floor muscle training for prevention and treatment of urinary and faecal incontinence in antenatal and postnatal women. Cochrane Database Syst Rev 10:CD007471PubMed
21.
Moore K, Dumoulin C, Bradley C, Burgio K, Chambers T, Hagen S, Hunter K, Imamaura M, Thakar R, Williams K, Vale L (2013) Adult conservative management. In: Abrams P, Cardozo L. Khouy S, Wein A (eds) Incontinence, 5th edn. IUCD, 5th International Consultation on Incontinence, Paris, pp 1101–1227
22.
Pelaez M, Gonzalez-Cerron S, Montejo R, Barakat R (2014) Pelvic floor muscle training included in a pregnancy exercise program is effective in primary prevention of urinary incontinence: a randomized controlled trial. Neurourol Urodyn 33:67–71CrossRefPubMed
23.
Arrue M, Diez-Itza I, Ibañez L, Paredes J, Murgiondo A, Sarasqueta C (2011) Factors involved in the persistence of stress urinary incontinence from pregnancy to 2 years post partum. Int J Gynaecol Obstet 115:256–259CrossRefPubMed
24.
Pizzoferrato AC, Fauconnier A, Quiboeuf E et al (2014) Urinary incontinence 4 and 12 years after first delivery: risk factors associated with prevalence, incidence, remission, and persistence in a cohort of 236 women. Neurourol Urodyn 338:1229–1234CrossRef
25.
Jango H, Langhoff-Roos J, Rosthoj S, Sakse A (2014) Modifiable risk factors of obstetric anal sphincter injury in primiparous women: a population-based cohort study. Am J Obstet Gynecol 210:59.e1–59.e6CrossRef
26.
Aasheim V, Nilsen BA, Lukasse M, Reinar ML (2011) Perineal techniques during the second stage of labour for reducing perineal trauma. Cochrane Database Syst Rev 12:CD006672
27.
Dahlen HG, Homer CS, Cooke M, Upton AM, Nunn R, Brodrick B (2007) Perineal outcomes and maternal comfort related to the application of perineal warm packs in the second stage of labor: a randomized controlled trial. Birth 34:282–290CrossRefPubMed
28.
29.
30.
Kearney R, Miller JM, Ashton-Miller JA, DeLancey JO (2006) Obstetric factors associated with levator ani muscle injury after vaginal birth. Obstet Gynecol 107:144–149CrossRefPubMedPubMedCentral
31.
Gartland D, Donath S, MacArthur C, Brown SJ (2012) The onset, recurrence and associated obstetric risk factors for urinary incontinence in the first 18 months after a first birth: an Australian nulliparous cohort study. BJOG 119:1361–1369CrossRefPubMed
32.
Verheijen EC, Raven JH, Hofmeyr GJ (2009) Fundal pressure during the second stage of labour. Cochrane Database Syst Rev 4:CD00606
33.
Lemos A, Amorim MM, Dornelas de Andrade A, de Souza AI, Cabral Filho JE, Correia JB (2015) Pushing/bearing down methods for the second stage of labour. Cochrane Database Syst Rev 10:CD009124
34.
Elvander C, Ahlberg M, Thies-Lagergren L, Cnattingius S, Stephansson O (2015) Birth position and obstetric anal sphincter injury: a population-based study of 113 000 spontaneous births. BMC Pregnancy Childbirth 15:252CrossRefPubMedPubMedCentral
35.
Bulchandani S, Watts E, Sucharitha A, Yates D, Ismail KM (2015) Manual perineal support at the time of childbirth: a systematic review and meta-analysis. BJOG 122:1157–1165CrossRefPubMed
36.
Carroli G, Mignini L (2009) Episiotomy for vaginal birth. Cochrane Database Syst Rev 1:CD000081
37.
38.
Gyhagen M, Bullarbo M, Nielsen TF, Milsom I (2014) Faecal incontinence 20 years after one birth: a comparison between vaginal delivery and caesarean section. Int Urogynecol J 25:1411–1418CrossRefPubMed
39.
Coats PM, Chan KK, Wilkins M, Beard RJ (1980) A comparison between midline and mediolateral episiotomies. Br J Obstet Gynaecol 87:408–412CrossRefPubMed
40.
Kalis V, Laine K, de Leeuw JW, Ismail KM, Tincello DG (2012) Classification of episiotomy: towards a standardisation of terminology. BJOG 119:522–526CrossRefPubMed
41.
Stedenfeldt M, Pirhonen J, Blix E, Wilsgaard T, Vonen B, Oian P (2012) Episiotomy characteristics and risks for obstetric anal sphincter injuries: a case–control study. BJOG 119:724–730CrossRefPubMedPubMedCentral
42.
O’Mahony F, Hofmeyr GJ, Menon V (2010) Choice of instruments for assisted vaginal delivery. Cochrane Database Syst Rev 11:CD005455
43.
44.
Volløyhaug I, Mørkved S, Salvesen Ø, Salvesen KÅ (2015) Forceps delivery is associated with increased risk of pelvic organ prolapse and muscle trauma: a cross-sectional study 16–24 years after first delivery. Ultrasound Obstet Gynecol 46:487–495CrossRefPubMed
45.
MacArthur C, Glazener C, Lancashire R, Herbison P, Wilson D (2011) Exclusive caesarean delivery and subsequent urinary and faecal incontinence: a 12 year longitudinal study. BJOG 118:1000–1007CrossRef
46.
Fernando RJ, Sultan AH, Kettle C, Thakar R (2013) Methods of repair for obstetric anal sphincter injury. Cochrane Database Syst Rev 2:CD002866
47.
Andrews V, Thakar R, Sultan AH (2009) Structured hands-on training in repair of obstetric anal sphincter injuries (OASIS): an audit of clinical practice. Int Urogynecol J Pelvic Floor Dysfunct 20:193–199CrossRefPubMed
48.
Browning A, Lewis A, Whiteside S (2014) Predicting women at risk for developing obstetric fistula: a fistula index?: an observational study comparison of two cohorts. BJOG 121:604–609CrossRefPubMed
49.
Gyhagen M, Bullarbo M, Nielsen TF, Milsom I (2013) A comparison of the long-term consequences of vaginal delivery versus caesarean section on the prevalence, severity and bothersomeness of urinary incontinence subtypes: a national cohort study in primiparous women. BJOG 120:1548–1555CrossRefPubMed
50.
Term Breech Trial 3-Month Follow-up Collaborative Group, Hannah ME, Hannah WJ, Hodnett ED, Chalmers B, Kung R, Willan A, Amankwah K, Cheng M, Helewa M, Hewson S, Saigal S, Whyte H, Gafni A (2002) Outcomes at 3 months after planned cesarean vs planned vaginal delivery for breech presentation at term: the international randomized Term Breech Trial. JAMA 287:1822–1831CrossRef
51.
Hannah ME, Whyte H, Hannah WJ, Hewson S, Amankwah K, Cheng M, Gafni A, Guselle P, Helewa M, Hodnett ED, Hutton E, Kung R, McKay D, Ross S, Saigal S, Willan A (2004) Term breech trial collaborative group maternal outcomes at 2 years after planned cesarean section versus planned vaginal birth for breech presentation at term: the international randomized term breech trial. Am J Obstet Gynecol 191:917–927CrossRefPubMed
52.
Handa VL, Pierce CB, Muñoz A, Blomquist JL (2015) Longitudinal changes in overactive bladder and stress incontinence among parous women. Neurourol Urodyn 34:356–361CrossRefPubMed
53.
Jelovsek JE, Piccorelli A, Barber MD, Tunitsky-Bitton E, Kattan MW (2013) Prediction models for postpartum urinary and fecal incontinence in primiparous women. Female Pelvic Med Reconstr Surg 19:110–118CrossRefPubMed
54.
Silver RM (2012) Implications of the first cesarean: perinatal and future reproductive health and subsequent cesareans, placentation issues, uterine rupture risk, morbidity, and mortality. Semin Perinatol 36:315–323CrossRefPubMed
55.
56.
Hagen S, Stark D (2011) Conservative prevention and management of pelvic organ prolapse in women. Cochrane Database Syst Rev 12:CD003882. 10.​1002/​14651858
57.
Hilde G, Stær-Jensen J, Siafarikas F, Ellström Engh M, Bø K (2013) Postpartum pelvic floor muscle training and urinary incontinence: a randomized controlled trial. Obstet Gynecol 122:1231–1238CrossRefPubMed
58.
Diokno AC, Sampselle CM, Herzog AR, Raghunathan TE, Hines S, Messer K, Karl C, Leite MC (2004) Prevention of urinary incontinence by behavioral modification program: a randomized, controlled trial among older women in the community. J Urol 171:1165–1171CrossRefPubMed
59.
Hagen S, Glazener C, McClurg D, Macarthus C, HerbisonP WD, Tooz-Hobson P, Bain C, Hay-Smith J, Collins M, Elders A (2014) A multicenter randomised controlled trial of a pelvic floor muscle training intervention for the prevention of pelvic organ prolapse (PREVPOL). Neurourol Urodyn 33:852–853
60.
Bø K (2004) Urinary incontinence, pelvic floor dysfunction, exercise and sport. Sports Med 34(7):451–464CrossRefPubMed
61.
Bø K (2015) Pelvic floor dysfunction, prevention and treatment in elite athletes. In: Bø K, Berghmans B, Mørkved S, van Kampen M (eds) Evidence based physical therapy for the pelvic floor—bridging science and clinical practice, 2nd edn. Elsevier, Amsterdam, pp 387–407
62.
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group, Sarma AV, Kanaya A, Nyberg LM, Kusek JW, Vittinghoff E, Rutledge B, Cleary PA, Gatcomb P, Brown JS (2009) Risk factors for urinary incontinence among women with type 1 diabetes: findings from the epidemiology of diabetes interventions and complications study. Urology 73:1203–1209CrossRef
63.
Prentice AM (2006) The emerging epidemic of obesity in developing countries. Int J Epidemiol 35:93–99CrossRefPubMed
64.
Vissers D, Neels H, Vermandel A, De Wachter S, Tjalma WA, Wyndaele JJ, Taeymans J (2014) The effect of non-surgical weight loss interventions on urinary incontinence in overweight women: a systematic review and meta-analysis. Obes Rev 15:610–617CrossRefPubMed
65.
Waetjen LE, Leung K, Crawford SL, Huang MH, Gold EB, Greendale GA (2013) Study of women’s health across the nation. Menopause 20:428–436PubMedPubMedCentral
66.
Legendre G, Ringa V, Panjo H, Zins M, Fritel X (2015) Incidence and remission of urinary incontinence at midlife: a cohort study. BJOG 122:816–824CrossRefPubMed
67.
Townsend MK, Danforth KN, Lifford KL, Rosner B, Curhan GC, Resnick NM, Grodstein F (2007) Incidence and remission of urinary incontinence in middle-aged women. Am J Obstet Gynecol 197:167.e1–167.e5CrossRef
68.
Maserejian NN, Minassian VA, Chen S, Hall SA, McKinlay JB, Tennstedt SL (2014) Treatment status and risk factors for incidence and persistence of urinary incontinence in women. Int Urogynecol J 25:775–782CrossRefPubMed
69.
Townsend MK, Matthews CA, Whitehead WE, Grodstein F (2013) Risk factors for fecal incontinence in older women. Am J Gastroenterol 108:113–119CrossRefPubMed
70.
Kudish BI, Iglesia CB, Sokol RJ, Cochrane B, Richter HE, Larson J, Hendrix SL, Howard BV (2009) Effect of weight change on natural history of pelvic organ prolapse. Obstet Gynecol 113:81–88CrossRefPubMedPubMedCentral
71.
Thom DH, Brown JS, Schembri M, Ragins AI, Subak LL, Van Den Eeden SK (2010) Incidence of and risk factors for change in urinary incontinence status in a prospective cohort of middle-aged and older women: the reproductive risk of incontinence study in Kaiser. J Urol 184:1394–1401CrossRefPubMedPubMedCentral
72.
73.
Chantereau P, Brieu M, Kammal M, Farthmann J, Gabriel B, Cosson M (2014) Mechanical properties of pelvic soft tissue of young women and impact of aging. Int Urogynecol J 25:1547–1553CrossRefPubMed
74.
Møller L, Lose G, Jørgensen T (2000) Risk factors for lower urinary tract symptoms in women 40 to 60 years of age. Obstet Gynecol 96:446–451CrossRef
75.
Byles J, Millar CJ, Sibbritt DW, Chiarelli P (2009) Living with urinary incontinence: a longitudinal study of older women. Age Ageing 38:333–338CrossRefPubMed
76.
Hannestad YS, Rortveit G, Daltveit AK, Hunskaar S (2003) Are smoking and other lifestyle factors associated with female urinary incontinence? the Norwegian EPINCONT study. BJOG 2003(110):247–254CrossRef
77.
78.
Jura YH, Townsend MK, Curhan GC, Resnick NM, Grodstein F (2011) Caffeine intake, and the risk of stress, urgency and mixed urinary incontinence. J Urol 185:1775–1780CrossRefPubMedPubMedCentral
79.
The Leicestershire MRC Incontinence Study Group; Dallosso HM, McGrother CW, Matthews RJ, Donaldson MMK (2003) The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int 92:69–77CrossRef
80.
Bortolotti A, Bernardini B, Colli E, Di Benedetto P, Giocoli Nacci G, Landoni M et al (2000) Prevalence and risk factors for urinary incontinence in Italy. Eur Urol 37:30–35CrossRefPubMed
81.
Cartwright R, Srikrishna S, Cardozo L, Gonzalez J (2007) Does diet coke cause overactive bladder? a 4-way cross over trial investigating the effect of carbonated soft drinks on overactive bladder symptoms in normal volunteers. 37th Annual Meeting of the International Continence Society. Neurourol Urodyn 26:626–627
82.
Thyssen HH, Clevin L, Olesen S, Lose G (2002) Urinary incontinence in elite female athletes and dancers. Int Urogynecol J Pelvic Floor Dysfunct 13:15–17CrossRefPubMed
83.
Nygaard IE (1997) Does prolonged high-impact activity contribute to later urinary incontinence? a retrospective cohort study of female Olympians. Obstet Gynecol 90:718–722CrossRefPubMed
84.
Shaw JM, Hamad NM, Coleman TJ, Egger MJ, Hsu Y, Hitchcock R, Nygaard IE (2014) Intra-abdominal pressures during activity in women using an intra-vaginal pressure transducer. J Sports Sci 32:1176–1185CrossRefPubMedPubMedCentral
85.
Weir LF, Nygaard IE, Wilken J, Brandt D, Janz KF (2006) Postoperative activity restrictions: any evidence? Obstet Gynecol 107:305–309CrossRefPubMed
86.
Woodman PJ, Swift SE, O’Boyle AL, Valley MT, Bland DR, Kahn MA, Schaffer JI (2006) Prevalence of severe pelvic organ prolapse in relation to job description and socioeconomic status: a multicenter cross-sectional study. Int Urogynecol J Pelvic Floor Dysfunct 17:340–345CrossRefPubMed
87.
Sampselle CM, Harlow SD, Skurnick J, Brubaker L, Bondarenko I (2002) Urinary incontinence predictors and life impact in ethnically diverse perimenopausal women. Obstet Gynecol 100:1230–1238PubMed
88.
Leicestershire MRC Incontinence Study Group, Dallosso HM, McGrother CW, Matthews RJ, Donaldson MM (2004) Nutrient composition of the diet and the development of overactive bladder: a longitudinal study in women. Neurourol Urodyn 23:204–210CrossRef
89.
Digesu GA, Verdi E, Cardozo L, Olivieri L, Khullar V, Colli E (2012) Phase IIb, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to determine effects of elocalcitol in women with overactive bladder and idiopathic detrusor overactivity. Urology 80:48–54CrossRefPubMed
90.
Badalian SS, Rosenbaum PF (2010) Vitamin D and pelvic floor disorders in women: results from the national health and nutrition examination survey. Obstet Gynecol 115:795–803CrossRefPubMed
91.
Aydogmus S, Kelekci S, Aydogmus H, Demir M, Yilmaz B, Sutcu R (2015) Association of antepartum vitamin D levels with postpartum pelvic floor muscle strength and symptoms. Int Urogynecol J 26:1179–1184CrossRefPubMed
92.
Robinson D, Cardozo L, Milsom I, Pons ME, Kirby M, Koelbl H, Vierhout M (2014) Oestrogens and overactive bladder. Neurourol Urodyn 33:1086–1091CrossRefPubMed
93.
Gold EB, Waetjen LE, Ye J, Feng WY, Johnson WO, Greendale GA, Sampselle CM, Sternfield B, Harlow SD, Study of Women’s Health Across the Nation (SWAN) (2009) Association between menopausal transition stages and developing urinary incontinence. Obstet Gynecol 114:989–998CrossRefPubMedPubMedCentral
94.
Metadata
Title
Prevention of pelvic floor disorders: international urogynecological association research and development committee opinion
Authors
Tony Bazi
Satoru Takahashi
Sharif Ismail
Kari Bø
Alejandra M. Ruiz-Zapata
Jonathan Duckett
Dorothy Kammerer-Doak
Publication date
01-12-2016
Publisher
Springer London
Published in
International Urogynecology Journal / Issue 12/2016
Print ISSN: 0937-3462
Electronic ISSN: 1433-3023
DOI
https://doi.org/10.1007/s00192-016-2993-9

Other articles of this Issue 12/2016

International Urogynecology Journal 12/2016 Go to the issue

Letter to the Editor

Reply to the letter to the editor on Prien-Larsen et al.: Influence of TVT properties of midurethral sling procedures: high-stiffness versus low-stiffness tape

Original Article

Assessing the use of the IUGA/ICS classification system for prosthesis/graft complications in publications from 2011 to 2015

Original Article

Measuring the impact of a posterior compartment procedure on symptoms of obstructed defecation and posterior vaginal compartment anatomy

Review Article

Role of diet in fecal incontinence: a systematic review of the literature

Clinical Opinion

Can pelvic floor dysfunction after vaginal birth be prevented?

Original Article

Quality of life outcomes in peri-urethral calcium hydroxylapatite injection